Upconverting Oil-Laden Hollow Mesoporous Silica Microcapsules for

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Cite This: ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

Upconverting Oil-Laden Hollow Mesoporous Silica Microcapsules for Anti-Stokes-Based Biophotonic Applications Hak-Lae Lee,† Jung Hwan Park,‡ Hyun-Seok Choe,† Myung-Soo Lee,† Jeong-Min Park,† Naoyuki Harada,∥ Yoichi Sasaki,∥ Nobuhiro Yanai,∥,⊥ Nobuo Kimizuka,∥ Jintao Zhu,§ Suk Ho Bhang,*,‡ and Jae-Hyuk Kim*,† †

Department of Chemical and Environmental Engineering, Pusan National University, Busan 46241, Korea School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Korea § School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China ∥ Department of Chemistry and Biochemistry, Graduate School of Engineering, Center for Molecular Systems (CMS), Kyushu University, 744 Moto-oka, Nishi-ku, Fukuoka 819-0395, Japan ⊥ PRESTO, JST, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan

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S Supporting Information *

ABSTRACT: A recyclable, aqueous phase functioning and biocompatible photon upconverting system is developed. Hollow mesoporous silica microcapsules (HMSMs) with ordered radial mesochannels were employed, for the first time, as vehicles for the post-encapsulation of oil phase triplet−triplet annihilation upconversion (TTA-UC), with the capability of homogeneous suspension in water. In-depth characterization of such upconverting oil-laden HMSMs (UC-HMSMs) showed that the mesoporous silica shells reversibly stabilized the encapsulated UC oil in water to allow efficient upconverted emission, even under aerated conditions. In addition, the UC-HMSMs were found to actively bind to the surface of human mesenchymal stem cells without significant cytotoxicity and displayed upconverted bright blue emission under 640 nm excitation, indicating a potential of our new TTAUC system in biophotonic applications. These findings reveal the great promise of UC-HMSMs to serve as ideal vehicles not only for ultralow-power in vivo imaging but also for stem cell labeling, to facilitate the tracking of tumor cells in animal models. KEYWORDS: upconversion, triplet−triplet annihilation, hollow mesoporous silica, post-encapsulation, bioimaging therefore diffuse to promote energy transfer.10,11 Largely, in the interest of biomedical and environmental applications where aqueous media are prevalent, the development of TTAUC systems that are readily suspended and function in oxygenrich aqueous environments is an important objective. The most widely applied technology to date, which involves embedding UC-chromophores within rigid/rubbery polymeric or silica-based nano/microparticles, has been employed to facilitate upconversion in aqueous phases.12−14 The incorporation of UC-chromophores into nanoparticles was first achieved by Monguzzi and co-workers,15 who reported a successful example of green-to-blue upconversion, by isolating an appropriate combination of sensitizer and acceptor dyes within highly crosslinked polymeric nanoparticles. When the triplet diffusion rates of UC-chromophores isolated in nanoparticles are considered, retardation of intermolecular collision and energy transfer in such rigid matrices are often

1. INTRODUCTION As a unique technique for generating higher energy photons by employing lower energy ones, photon upconversion (UC) has drawn increasing research interest, due to its potential to enhance the efficiencies of solar-based technologies such as solar cells1−3 and photocatalysis,4 as well as to explore unconventional in vivo drug photorelease5 and other biophotonic applications.6−8 Boasting the advantage of high quantum yield at noncoherent, low excitation intensity close to sunlight, UC based on triplet−triplet annihilation (TTA) is an excellent candidate among various UC mechanisms for many of the aforementioned applications.9 In a typical TTA-UC process, the photoexcited sensitizers first enable energy transfer to acceptors by intermolecular triplet−triplet energy transfer (TTET), which subsequently triggers bimolecular TTA between the two triplet acceptors to produce one singlet acceptor of higher energy. Since molecular collisions and triplet diffusion among transient species are essential to realizing TTET and TTA, previous research into TTA-UC has focused on liquid organic solvents and rubbery polymeric media in which the organic chromophores are soluble, and can © XXXX American Chemical Society

Received: April 15, 2019 Accepted: July 5, 2019 Published: July 5, 2019 A

DOI: 10.1021/acsami.9b06620 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

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ACS Applied Materials & Interfaces

Figure 1. Schematic of the proposed post-encapsulation strategy of employing HMSM as a vehicle for aqueous phase TTA-UC.

Through the highly porous mesochannels on the silica shells, the UC oil was infused into the HMSMs, followed by centrifugation to obtain a homogeneous aqueous suspension (denoted as “UC-HMSMs”, Figure 1). Based on this simple yet robust method to encapsulate the UC oil in the HMSMs, a new and general platform for aqueous phase photon upconversion could be realized in an effective and scalable manner. The superior features of the prepared materials were further illustrated in four ways. (1) Radially ordered mesopores enable the UC oil in bulk solution to infuse through their intact shells without any fastidious chemical or thermal treatment, thus helping to preserve the photochemical characteristics of UC-chromophores even after encapsulation. (2) The large interior cavities of the HMSMs serve as excellent reservoirs for the storage of the UC oil at high loadings, thereby facilitating strong UC emission, even under a low excitation power source, such as an LED. (3) Owing to the open mesochannels, the encapsulated UC oil is easily removed from the inner cores of the capsules, which facilitates further promising functions as recyclable and core flexible TTA-UC vehicles. (4) The general synthetic strategy of the HMSMs enables the inclusion of metal nanoparticles in their interior void space for multiple unique functionalities. To advance this UC-HMSM technology and examine its potential for future developments in prospective biophotonic applications, we further demonstrated that the specific concentration of UCHMSMs can successfully be tagged on the surface of human mesenchymal stem cells (hMSCs) without significant cytotoxicity, and these UC-tagged hMSCs exhibit upconverted blue emissions upon excitation at 635 nm. Hence, they can potentially be employed as biocompatible cell-mediated TTA-UC carriers capable of working at low-power excitation for tumor-targeted bioimaging.

tradeoffs in this strategy, despite their very appealing abilities to protect against oxygen quenching. In the same year, we reported the successful microfluidic emulsification of a UCchromophore-containing HD/PIB mixture within a photocurable polymeric shell.4 Unfortunately, this microemulsionbased TTA-UC system inherently suffered from unfavorable particle sizes for biomedical applications (∼200 μm or larger in diameter), and the inevitable damage to the UC-chromophores by radicals produced during the shell polymerization process. A more promising approach to an aqueous phase TTA-UC was demonstrated by Kwon, in which UC-chromophore-containing organic media were encapsulated within inorganic silica shells to form core−shell structures.16 However, the major drawbacks included the lack of reaccessibility and modifiability of the embedded chromophore, as well as the vulnerability and loss of the UC medium during the encapsulation process, which hampers their ability to function as efficient TTA-UC vehicles. More recently, mesoporous silica spheres were shown to successfully adsorb UC-chromophores through their radially ordered mesochannels, to realize a TTA-UC in aqueous suspension.5 Despite the promising post-encapsulation strategy provided by the highly accessible mesostructure, the loading capacity of the silica nanoparticles requires improvement. These challenges inspired us to develop an ideal TTA-UC vehicle, in which the encapsulation of UC-chromophores at high loading capacities could be controlled. Such a vehicle would further advance this field. This goal is achieved in the current work by a simple strategy to employ hollow mesoporous silica microcapsules (HMSMs) as vehicles for aqueous phase photon upconversion. The highly porous features and hollow cavities of the HMSMs facilitate the facile post-encapsulation of a TTA-UC medium at high loadings. Highly uniform HMSMs with tunable diameters of 1.0−1.8 μm were first fabricated by a surfactant-assisted Stöber method and a subsequent self-transformation approach. B


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to remove excessive reactants. The washing step was repeated several times, and the product was finally redispersed in deionized water for further use. 2.5. Materials Characterization. The morphologies and structural properties of the prepared materials were characterized by field emission scanning electron microscopy (SEM, SUPRA 25, EDAX, Carl Zeiss Co., Germany). Field emission transmission electron microscopy (TEM, TALOS F200X, Thermo Fisher Scientific Co.) combined with energy-dispersive X-ray (EDX) spectroscopy was employed for structural and qualitative elemental analyses. The particle size distribution of HMSMs dispersed in ethanol was determined using a particle size analyzer (LS 13 320, Beckman Coulter Co.). To determine the crystalline phase of the HMSMs, they were subjected to wide-angle X-ray diffraction using an Xpert 3 diffractometer (Malvern Panalytical Ltd., U.K.) with Cu Kα radiation at 40 kV and 40 mA. To investigate the densities of HMSMs on the nanoscale, small-angle X-ray scattering data were collected in a continuous scan mode in the 1−10° range with a 0.01° sampling interval. Brunauer−Emmett−Teller (BET) specific surface areas were determined by adsorption analysis using an ASAP 2020 Plus physisorption system (Micromeritics Instrument Co.). Pore size distributions were calculated from the desorption branches of the isotherms by the Barrett−Joyner−Halenda method. Room-temperature magnetism was determined using a magnetic property measurement system (MPMS-7, Quantum Design Inc). Microscopic images were obtained using a microscope (T550B, Amscope) with ×100 objective lens. 2.6. Photoluminescence Measurements. Static absorption and Stokes emission spectra were acquired and analyzed using a spectrofluorometer (FS5-MCS, Edinburgh Instruments, U.K.). AntiStokes emission spectra were acquired using a custom laser setup, in which UC samples were excited at an angle of approximately 45°, using a 635 nm commercial diode laser with a 4 mm diameter beam. The emission was modulated with an optical chopper (80 Hz), directed to a monochromator (Oriel Cornerstone, Newport Corporation) using a series of focusing lenses, and scattered laser light was removed using a 632.8 nm notch filter. The signal was then detected using an Oriel photomultiplier tube, and processed by a lockin amplifier (SRB10 DSP, Stanford Research Systems). The incident laser intensity was adjusted using a continuously variable neutral density filter and measured using a power meter (843-R, Newport Corporation). The shelf life of UC-HMSMs aqueous suspension was measured by recording the UC emission intensity (470 nm) every 24 h using 66.6 mW cm−2 laser excitation at 635 nm. The intensity was recorded through the time-interval scanning mode and the average value over 1−5 min was used for the data. The quantum yields of TTA-UC emission were measured using an absolute quantum yield measurement system Quantaurus-QY Plus installed with a multichannel detector C13534-01 (Hamamatsu Photonics, detection wavelength from 300 to 950 nm). The samples were held in an integrating sphere and excited by the laser source (635 nm, 75 mW, RGB Photonics) through a focusing lens. The laser power was controlled by combining a software (Ltune) and neutral density filters and measured using a PD300-UV photodiode sensor (OPHIR Photonics). The diameter of the laser beam (1/e2) was estimated to be 1.5×10−4 cm2 using a charge-coupled device beam profiler SP620 (OPHIR Photonics). The scattered excitation light was removed using a 575 nm shortpass filter, and the emitted light was monitored with a multichannel detector. The spectrometer including the integration sphere and shortpass filter was calibrated by Hamamatsu Photonics. Time-resolved photoluminescence lifetime measurements were carried out using a time-correlated single-photon counting lifetime spectroscopy system Quantaurus-Tau C11567-01 (Hamamatsu Photonics). Confocal laser scanning microscopy (CLSM) images were acquired using a confocal laser scanning microscope (LSM 800, Carl Zeiss Co., Germany). In detail, a small amount of the UC-HMSMs aqueous suspension (5 mg/mL) was casted on a 0.13 mm thick slide glass (24 mm × 60 mm) and covered with a 0.13 mm thick cover glass (22 mm × 22 mm). One droplet of emulsion oil was placed onto the ×63 objective lens, and the sample was observed

2. EXPERIMENTAL SECTION 2.1. Materials. Tetraethyl orthosilicate (TEOS), hexadecyltrimethylammonium bromide (CTAB), trisodium citrate, oleic acid (technical grade, 90%), tetrahydrofuran (THF), and perylene were purchased from Sigma-Aldrich. Methanol (99.9%), ethylene glycol (99.5%), ammonia solution (28−30%), sodium acetate, iron(III) chloride, and ammonium nitrate were purchased from Samchun Chemicals. All chemicals were used as received. Palladium(II) mesotetraphenyltetrabenzoporphyrin (PdTPBP) was synthesized according to a procedure in the literature.17 2.2. Synthesis of Hollow Mesoporous Silica Microcapsules (HMSMs). Mesoporous silica microspheres (MSMs) with a mean diameter of 1.8 μm were prepared by a surfactant-assisted sol−gel process in a Stöber solution containing CTAB, TEOS, ammonia, and methanol. In a typical procedure, a methanolic solution of CTAB (3.5 mL, 20 mg/mL) was added into a 50 mL falcon tube containing a mixture of methanol (25.63 mL), deionized water (7.7 mL), and concentrated ammonia solution (1.75 mL). A methanolic solution of TEOS (1.4 mL, 5:5) was then rapidly injected into the mixed solution with slight shaking, and the reaction was allowed to proceed for 12 h at room temperature (RT) under static conditions, after which the clear supernatant was removed, and the pellet was redispersed in methanol, sonicated for 5 min, and collected by filtration. The Stöberderived silica product was then dispersed in 20% ethanol/water, to prepare HMSMs using the self-transformation approach. Specifically, the mixture was incubated at 70 °C for 6 h, after which the solid was collected by filtration, and washed several times with ethanol. The obtained product was calcined in a high-temperature electric furnace (FTSIF-705, SCI Finetech Co., Korea) at 550 °C for 6 h, at a ramp rate of 5 °C min−1, to remove the pore-generating CTAB template. 2.3. Synthesis of Yolk−Shell Structured Magnetic Silica Microcapsules (YMSMs). Magnetite nanoparticles with a mean diameter of 200 nm were prepared by a modified solvothermal method.18 Briefly, FeCl3 (3.0 g), sodium acetate (5.0 g), and trisodium citrate (0.7 g) were dissolved in ethylene glycol (80 mL) with magnetic stirring. The resulting solution was transferred to and sealed in a 100 mL Teflon-lined stainless steel autoclave, which was heated at 200 °C in the above-mentioned high-temperature electric furnace for 10 h, after which it was allowed to cool naturally to RT. The black Fe3O4 particles were collected with a magnet and washed several times with deionized water and ethanol. The product was finally dried at RT for 12 h. The prepared Fe3O4 nanoparticles were used to prepare core−shell Fe3O4@mSiO2 composites with a mean diameter of 1.8 μm through a surfactant-assisted sol−gel process. Typically, a methanol solution of CTAB (2.5 mL, 20 mg/mL) was added into a 50 mL falcon tube containing a mixture of the Fe3O4 nanoparticles (5 mg), methanol (19 mL), deionized water (5 mL), and concentrated ammonia solution (1.75 mL). A methanolic solution of TEOS (0.8 mL, 5:5) was then rapidly injected into the mixed solution with slight shaking, and the reaction was allowed to proceed for 12 h at RT under static conditions, after which the clear supernatant was removed, and the pellet was redispersed in methanol, sonicated for 5 min, and collected by filtration. The obtained product was then incubated in 10% ethanol/water at 70 °C for 48 h. Ammonium nitrate was used to extract the pore-generating CTAB template by fast ion exchange, according to a procedure in the literature.19 Briefly, the as-obtained product was treated with an ethanolic solution of ammonium nitrate (100 mL, 6 mg/mL) at 60 °C for 3 h. The extraction step was repeated twice, to ensure the complete removal of CTAB. The obtained YMSMs were finally collected using a magnet and washed several times with ethanol. 2.4. Preparation of UC Oil-Encapsulated HMSMs/YMSMs (UC-HMSMs/YMSMs). PdTPBP (2 mg) and perylene (20 mg) were dissolved in THF (4 mL) prior to the preparation of the UC oil, after which OA (5 mL) was added to the as-prepared solution, and stored at 70 °C in an oven overnight, to completely evaporate the THF solvent. To encapsulate the obtained UC oil, HMSMs or YMSMs (40 mg) were dispersed in the prepared UC oil (0.4 mL), and the mixture was vigorously stirred in the dark at RT for 2 h. The obtained product was then collected by centrifugation and washed with deionized water C


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Figure 2. (A) SEM and (B) TEM images of HMSMs obtained via the surfactant-assisted Stöber method in a methanol/water solution and a subsequent self-transformation approach. The inset in (A) shows the SEM image of a crushed particle. (C) High-magnification TEM image of an HMSM shell. (D) Nitrogen sorption isotherm and pore size distribution curve (inset) of the HMSMs. (E) Small-angle X-ray scattering and X-ray diffraction (XRD) (inset) patterns of the HMSMs. Scale bars in (A), (B), and (C) represent 1 μm and 50 nm, respectively. 30 s), annealing (55 °C, 30 s), and extension (72 °C, 45 s), and a final extension at 72 °C for 10 min, were performed. The PCR results were visualized by electrophoresis on 1.5% (w/v) agarose gel with RedSafe Nucleic Acid Staining Solution (iNtRON Biotechnology, Korea). The results were examined using a gel documentation system (WGE-30, Daihan Scientific Co. Ltd., Korea). The BCL-XL primer sequence was: sense, 5′-CGG GCA TTC AGT GAC CTG AC-3′; antisense, 5′TCA GGA ACC AGC GGT TGA AG-′3, while that of BAX was: sense, 5′-GTG CAC CAA GGT GCC GGA AC-3′; antisense, 5′TCA GCC CAT CTT CTT CCA GA-3′. β-Actin served as the internal control (sense, 5′-GCA CTC TTC CAG CCT TCC TTC C3′; antisense, 5′-TCA CCT TCA CCG TTC CAG TTT TT-3′). 2.9. In Vitro TTA-UC Experiments. The hMSCs were cultured on a 150 mm dish (1 × 106 cells/well) and incubated with 200 μg mL−1 UC-HMSMs for 24 h. The cells were then rinsed seven times with PBS to completely remove excess UC-HMSMs that were not attached to the hMSCs. The hMSCs treated with the UC-HMSMs were then detached from the cell culture dish using trypsin-EDTA (Gibco BRL), after which the hMSCs were collected by low-speed centrifugation. The centrifuged cells were redispersed in a 200 μL microcentrifuge tube, and irradiated with a 635 nm diode laser. A digital photograph depicting the TTA-UC in the sample was obtained through a 500 nm shortpass filter. CLSM images were acquired using a confocal laser scanning microscope (LSM 710, Carl Zeiss Co., Germany). 3. Results and Discussion. 3.1. Synthesis and Characterization of Hollow Mesoporous Silica Microcapsules. The synthetic strategy for the HMSMs is depicted in Figure S1. First, mesoporous silica microspheres (MSMs) were prepared using a surfactant-assisted Stöber method in methanol/water solution. It is well-known that the incorporation of a cationic surfactant in the Stöber solution provides a source of micelles that play crucial roles during the formation of MCM-41.20 Hexadecyltrimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS) were used as the mesopore-directing cationic surfactant and soluble silica precursor, respectively. The Stö ber-derived MSMs were then hydrothermally treated in ethanol/water solution (20 vol %) at 70 °C to selectively etch out their structurally more condensed inner sections, a process that transforms the solid spheres into hollow

through differential interference contrast (DIC) and the 450−550 nm fluorescence channel. The detailed acquisition information is as follows: pinhole: 56 μm, laser: 640 nm (10.00%), detector gain: 900 V, detector offset: 0, detector digital gain: 2.0. 2.7. Cell Culture and Cytotoxicity Experiments. hMSCs (Lonza, Basel, Switzerland) were cultured in Dulbecco’s modified Eagle medium (DMEM, Gibco BRL, Gaithersburg, MD) and supplemented with 10% (v/v) fetal bovine serum (Gibco BRL) and 1% (v/v) penicillin−streptomycin (Gibco BRL). The medium was changed every 2 days. After six refresh cycles, the hMSCs were used in experiments. For cytotoxicity experiments involving the HMSMs and UC-HMSMs, the cell viability tests were performed using Cell Counting Kit-8 (CCK-8). Briefly, the hMSCs were cultured on a 24well plate (1 × 104 cells/well) incubated with different concentrations of HMSMs or UC-HMSMs for 24 h, prior to adding DMEM and a 10% (v/v) CCK-8 solution to the culture. After incubation at 37 °C for 2 h under 5% CO2, the absorbance was measured at 450 nm using an Infinite F50 microplate reader (Tecan Trading AG, Switzerland). hMSC viability was expressed as a percentage against a normal hMSC (no treatment) group. 2.8. Apoptotic Activity Experiments. The hMSCs were cultured in six-well plates (1 × 105 cells/well) for 24 h, and then separately incubated with 200 μg mL−1 of HMSMs and UC-HMSMs for an additional 24 h, prior to apoptotic activity testing. Live/dead cells were examined using fluorescein diacetate (FDA, 5 mg mL−1) and ethidium bromide (EB, 10 μg mL−1) staining. Specifically, hMSCs treated with 200 μg mL−1 of HMSMs and UC-HMSMs were incubated in FDA−EB solution for 5 min at 37 °C and rinsed with phosphate-buffered saline (PBS). The stained cells were examined by fluorescence microscopy. Apoptotic activity was evaluated using a reverse transcriptase polymerase chain reaction (RT-PCR). Total RNA was extracted from the specimens with chloroform and precipitated with isopropanol. After removal of the supernatant, the RNA pellets were washed with 75% (v/v) ethanol, air-dried, and dissolved in 0.1% (v/v) diethyl-pyrocarbonate-treated water. A 1 μL aliquot of pure total RNA and Prime Script RT master mix (TaKaRa Clontech, Japan) was used for reverse transcription. The synthesized complementary DNA was amplified by the polymerase chain reaction (PCR). During the PCR process, thirty cycles of denaturing (94 °C, D


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Figure 3. CLSM images and the corresponding fluorescence (450−550 nm) and DIC profiles of (A, C) perylene-HMSMs and (B, D) UC-HMSMs under 405 nm (top) and 640 nm (bottom) laser excitation. The images in (A−D) are merged images of bright-field and fluorescence channel (450−550 nm). The intensity profiles were obtained from the red dotted lines. [PdTPBP] = 0.43 mM and [perylene] = 39.6 mM in encapsulated OA. Scale bars represent 5 μm. structures. It is worth noting that the inclusion of a small amount of ethanol in the solution helps to prevent the aggregation of the dispersed particles, as well as the redeposition of dissolved silica species on the outermost shells during the self-transformation process, which would otherwise clog the mesopores, and hamper the infusion of the UC oil. Finally, the pore-directing CTAB template was removed by calcination, resulting in surfactant-free HMSMs. The MSMs were clearly observed to transform from solid to hollow structures after incubation in 20% ethanol/water solution for 6 h, and no broken spheres were observed, even after calcination at 550 °C for 6 h (Figures 2A,B, and S2). The sizes of the HMSMs can be precisely modulated by controlling the amount of deionized water in the Stöber solution (Figure S3). Particle size analysis (Figure S4) also confirms the narrow size distribution of the prepared HMSMs. In particular, the average size of the HMSM particles increased from 1.2 to 1.8 μm as the water content in the Stöber solution was decreased from 10.7 to 7.7 mL. This increase in size is largely due to the slower hydration and nucleation rates resulting from a decrease in the number of hydroxyl groups at lower water concentrations in the medium. The highmagnification TEM image (Figure 2C) reveals that the HMSM mesochannels are radially oriented toward the surface, a structure that favors the infusion of guest molecules, such as sensitizers and acceptors.

Energy-dispersive X-ray (EDX) spectra and maps of the HMSMs (Figure S5), which qualitatively identify the presence and distributions of elements, confirm that the HMSMs are composed of Si and O. The nitrogen sorption isotherm of the HMSMs (Figure 2D) exhibits a type IV curve with a hysteresis loop that gradually closes at a partial pressure near 0.4, which is characteristic of a high surface area and narrow pore size distribution. The BET surface area and pore volume of the HMSMs were calculated to be 823.66 m2 g−1 and 0.53 cm3 g−1, respectively. The pore size distribution graph (inset in Figure 2D) reveals that the HMSM mesopores are uniform and have a mean diameter of about 2 nm. These silica framework mesopores exclusively facilitate access by water molecules, which enables the transfer of silica species from the inner to the outer regions during the self-transformation process.21 The small-angle Xray scattering pattern of the HMSMs (Figure 2E) shows three diffraction peaks that are associated with 100, 110, and 200 reflections of hexagonal symmetry, which confirm the regular mesoporous arrangement in the silica framework.22 These results reveal that the MCM-41 support of the MSM remains structurally unchanged, even after the solid-to-hollow structural transformation. The XRD pattern (inset in Figure 2E) shows a broad diffraction peak in the 12−38° range, which indicates that the HMSMs are amorphous. E


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Figure 4. (A) Emission profiles of aqueous suspensions containing HMSMs only, perylene-HMSMs, PdTPBP-HMSMs, and UC-HMSMs under 635 nm laser excitation. Inset in (A) shows the digital image of UC-HMSMs suspension under white light (left) and 635 nm laser excitation (right). (B) Digital images of aqueous suspensions containing HMSMs only, perylene-HMSMs, PdTPBP-HMSMs, and UC-HMSMs under white light (left) and 628 nm LED excitation (right). The digital images in (A) (inset, right) and (B) (right) were acquired through a 500 nm shortpass ′ (λex = 635, 575 nm shortpass filter) and (D) UC emission decay (λex = 630 nm, λem = 440, 510 nm shortpass filter) profiles of the filter. (C) ΦUC bulk UC oil and UC-HMSMs aqueous suspension. CLSM images of (E) UC-HMSMs containing PdTPBP and perylene ([PdTPBP] = 0.43 mM and [perylene] = 39.6 mM in encapsulated OA), (F) HMSMs after washing with ethanol, and (G) UC-HMSMs refilled with PdTPBP and 9,10bis(phenylethynyl)anthracene (BPEA) ([PdTPBP] = 0.43 mM and [BPEA] = 26.4 mM in encapsulated OA). Scale bars in (E−G) represent 5 μm. 3.2. Post-Encapsulation of UC Oil into HMSMs. To examine their effectiveness as TTA-UC vehicles, the HMSMs were filled with an oil containing palladium(II) meso-tetraphenyltetrabenzoporphyrin (PdTPBP) as a sensitizer, and perylene as an acceptor. Oleic acid (OA) was chosen as the oily medium for the TTA-UC because it is well-known to be a reductive solvent that consumes generated singlet oxygen, which protects the sensitizer from oxidation and maintains high TTA-UC stability even under oxygen-rich conditions.12 The normalized absorption and emission spectra of PdTPBP and perylene and a schematic of the TTA-UC mechanism are shown in Figures S6 and S7, respectively. Figure S8A reveals that after vigorous stirring for 2 h, the translucent HMSM and TTA-UC mixture transformed into a semi-transparent solution, which indicates that the inner cavities of the HMSMs were completely filled with the TTA-UC solution, resulting in a lower difference in the refractive indices of the inner and outer sections of the HMSMs. Interestingly, after the mixture was poured over deionized water, the oil-laden HMSMs could easily be separated from the excess oil phase under a centrifugal force, leading to the formation of a homogeneous UC-HMSMs aqueous suspension. The successful encapsulation of the UC oil into the HMSMs was confirmed by bright-field microscopy. Compared with the water-filled HMSMs (Figure S8B, left), the UC-HMSMs (Figure S8B, right) clearly exhibited larger contrast differences between the cores (dark gray) and outer sites (gray), due to the larger difference in the refractive index of the encapsulated OA and the outer water. Also, note that after the post-encapsulation step, there was no agglomeration of the capsules, which has been considered to be one

of the drawbacks of mini-emulsion-based UC nanocapsules synthesis.13,16,23 Moreover, the encapsulated UC oil seldom escaped from the core even after being stored in water for 5 days (Figure S9), which is ascribed to the large difference in hydrophobicity between the encapsulated OA and the outer water. The unique oil-laden HMSM structure reported in the current work can contribute to developing a new generation of an oil-in-water emulsion system with a convenient preparation method. 3.3. TTA-UC Performance of UC-HMSMs. To verify that the obtained UC-HMSMs display upconverted fluorescence, the water suspension of UC-HMSMs was visualized by confocal laser scanning microscopy (CLSM), with the channel set to the 450−550 nm range, which corresponds to the fluorescence band of perylene. HMSMs filled only with perylene (perylene-HMSMs) were also examined for comparison. When irradiated with a 405 nm laser, the blue Stokes emission of perylene was clearly observable from both the peryleneHMSMs and UC-HMSMs (Figure 3A,B). In contrast, the UCHMSMs only exhibited bright blue emissions when irradiated with a 640 nm laser, while the perylene-HMSMs exhibited no fluorescence (Figure 3C,D), which verifies that the perylene fluorescence observed in the UC-HMSMs resulted from the TTA-UC process. Meanwhile, an overlay of the bright-field and fluorescence channel images unambiguously reveals that the intense blue emissions originate from the cores of the UC-HMSMs (Figure S10). The emission profiles of fluorescence (450−550 nm) and DIC channels also reveal that strong, intense emission appears only in the core region, which is comparable to the sharp decrease in the DIC channel, thus reconfirming that the F


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ACS Applied Materials & Interfaces encapsulated UC oil is clearly stabilized by the mesoporous silica shells in water. Consistently, the UC spectra from the UC-HMSMs clearly matched that of the perylene fluorescence, whereas the control samples of chromophore-free HMSMs, perylene-HMSMs, and PdTPBP-HMSMs showed no UC emissions under equivalent excitation, reconfirming that the blue emission from the UCHMSMs is exclusively the result of the TTA-UC process (Figure 4A). Furthermore, the bright blue emission from the water suspension of UC-HMSMs was clearly visible to the naked eye through a 500 nm shortpass filter, even under the ultralow-power excitation with 628 nm LED (23.3 mW cm−2, Figure 4B). The mechanism of TTA-UC operation was further evidenced by the excitation power dependence of UC emission intensity (Figure S11). In the typical TTA-UC systems, the UC emission intensity shows a quadratic and linear dependence on the incident light intensity at low- and high-intensity ranges, respectively.10 Indeed, in our aqueous phase TTA-UC system, the UC emission intensity gradually transitioned from a quadratic (slope = 2.0) to a nearly linear (slope = 1.4) dependence on excitation power. This characteristic transition reflects the fact that under weak excitation, the dominant mechanism for depopulation of the acceptor’s triplet states is pseudo-first-order decay and thus the UC emission intensity displays a quadratic dependence on excitation power as expected for a bimolecular process. However, under a relatively higher excitation power, TTA overtakes the pseudo-firstorder decay and the TTA-UC intensity becomes linearly dependent on excitation power. Although the slope of linear fit at 100 mW cm−2 still remains about 1.4 in our system, considering that it is difficult to achieve complete linear power dependence with the aqueous suspension of UC capsules due to significant light scattering, the HMSMs are expected to serve as a useful platform for effective aqueous phase TTA-UC. The UC quantum yield of the UC-HMSMs aqueous suspension was then measured as a function of the excitation power using an absolute quantum yield measurement setup with an integrating sphere (Figure 4C). The UC quantum yield of the bulk UC oil was also measured for comparison. Note that the TTA-UC is a bimolecular process that uses two photons to produce one higher energy photon and thus the theoretical maximum ΦUC is 50%.24,25 To avoid confusion, it is written as Φ′UC (=2ΦUC) when the maximum yield is standardized to be 100%. ′ value of the UC-HMSMs aqueous suspension, in The highest ΦUC which the bulk UC oil droplets are surrounded by the mesoporous silica shells in the oxygen-rich aqueous environment, was measured to be 0.3%, which is a 10-fold smaller value than that of the bulk UC oil (3.4%) at the equivalent excitation power. The difference in the quantum yields of bulk UC oil and UC-HMSMs aqueous suspension is also reflected in the UC lifetime shown in Figure 4D. The perylene triplet lifetime τT of the UC-HMSMs was measured to be 82 μs, much shorter than that of the bulk UC oil (388 μs), by the tail fitting of the emission decay profile according to the known relationship, IUC(t) ∝ exp(−t/τUC) = exp(−2t/τT), where τUC is the UC emission lifetime.11,26 These results indicate that the excited triplet state in the encapsulated UC oil is partly quenched when it is surrounded by the mesoporous silica shells in the oxygen-rich environment. To further understand the quenching of the UC emission, the stabilities of bulk UC oil and UC-HMSMs aqueous suspensions with and without deaeration were measured under continuous excitation by the 635 nm laser (Figure S12). The bulk UC oil retained 19% of the original UC emission after 4500 s. While unsaturated carbons in OA could capture the produced singlet oxygens to enable the TTET from sensitizers to acceptors, the decreased UC emission intensity of air-saturated bulk UC oil is ascribed to the continuous inflow of oxygen species from the entire solution into the laser pathway. On the other hand, the UC emission intensities of UC-HMSMs aqueous suspensions both with and without deaeration remained steady during 4500 s of continuous irradiation at 66.6 mW cm−2, supporting that the mesoporous silica shells acted as an effective oxygen barrier for the encapsulated UC oil core. Furthermore, the UC-HMSMs aqueous suspension retained

71% of the original UC emission even after 120 h of storage at room temperature, which also underlines its fair long-term durability even in the oxygen-rich aqueous environment (Figure S13). From these results, it is evident that although the UC emission of the UC oil is partly quenched when encapsulated into HMSMs, the mesoporous silica shells provide an air-sealing effect to maintain about 10% UC capabilities of the encapsulated UC oil even in the oxygen-rich aqueous environment without any additional surface treatment. Considering that strict deoxygenation treatment has been necessary to realize solution-phase TTA-UC, which severely hampers their reallife applications,27,28 we believe that the current post-encapsulation approach with the HMSMs gives a simple and general platform to achieve aqueous TTA-UC in air for wide applications in oxygensensitive photochemistry, theranostics, and studies in many disciplines. The superior modifiability of the UC-HMSMs was further demonstrated by simply incorporating superparamagnetic magnetite nanoparticles in the void space of the HMSMs, to provide multifunctionalities. To date, the incorporation of functional metal cores inside the UC capsules for multiresponsiveness has never been attempted. Yolk−shell structures, also known as the “rattle-type structure”, represent a new class of core−shell structure with typical core@void@shell configurations, and they usually offer better potentials than simple core−shell structures. As the core nanoparticles are encapsulated and move freely inside the hollow shells, the system possesses the advantages of both hollow and core−shell structures. With the rapid development of a variety of applications, the inclusion of superparamagnetic magnetite nanoparticles in the HMSMs endows the resulting composite, which is widely known as magnetic yolk− shell-structured mesoporous silica microcapsules (YMSMs), with multiple unique functionalities, such as magnetic targeting, convenient magnetic separation, and magnetic resonance imaging capabilities.29,30 The YMSMs were first synthesized by a surfactant-assisted Stöber method and a subsequent self-transformation approach (Figure S14A). The TEM (Figure S14B−D) and EDX (Figure S15) images clearly confirm the successful formation of yolk−shell structures with magnetite cores and mesoporous silica shells. The saturation magnetization values of the bare Fe3O4 nanoparticles and YMSMs were measured to be ∼57.3 and 6.35 emu g−1, respectively (Figure S16). After post-encapsulation of the UC oil into the YMSNs (denoted as “UC-YMSMs”), the upconverted emission spectra from the water suspension of UC-YMSMs upon laser excitation at 635 nm were clearly observed (Figure S17). In addition, the magnetic responsivities of the UC-YMSMs facilitate their rapid and convenient separation from the medium by a magnet (Video S1), widening the potential of our UC system in multifunctional applications. It is worth mentioning that our post-encapsulation-based approach toward an aqueous phase TTA-UC is novel, and has several distinct advantages over many previously reported strategies that were based on the pre-encapsulation of UC-chromophores. First, the UC oil remains almost intact during the encapsulation process, since it requires no fastidious chemical reactions, such as radical polymerization, hydro-condensation, or thermal treatment, which can damage the UC-chromophores, and thereby greatly lower TTA-UC efficiency.31−33 The radially ordered mesopores in the HMSMs exclusively enable the UC oil in the bulk solution to readily infuse into the inner cavity without any chemical or thermal treatment, while preserving the photochemical properties of the HMSMs. Second, the impregnation efficiency (g oil/g vehicles × 100%) of the HMSMs (133.7%) is 1.8 times higher than that of the MSMs (73.0%), due to their unique hollow structures (Figure S18) that provide remarkably enhanced loading capacities for guest molecules. Third, when washed with amphiphilic solvents, such as ethanol, the encapsulated UC oil can be easily removed from the core, which provides an opportunity to fine-tune the sensitizer/acceptor couple for further use. To prove the reusability of the HMSMs, the UC-HMSMs were washed with ethanol and then refilled with a UC oil containing PdTPBP as a sensitizer and 9,10-bis(phenylethynyl)anthracene (BPEA) as an acceptor for red-to-green TTA-UC. As shown in the CLSM images (Figure 4E,F), upon 640 nm excitation, the upconverted blue G


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capsules and their applications in biomedical fields,36,39,40 but to the best of our knowledge, there are not many works that have deeply investigated the cytotoxicity of the fabricated silica-based UC capsules to prove reasonable biomedical applicabilities. Even at HMSM and UC-HMSM concentrations of 200 μg mL−1, neither one exhibited any cytotoxicity, when compared to the viability in the absence of treatment (NT). Cell viability and apoptotic activity were then further assessed through fluorescein diacetate−ethidium bromide (FDA−EB) staining and the reverse transcriptase polymerase chain reaction (RTPCR) technique, respectively. FDA−EB staining revealed no cell death when the hMSCs were treated with 200 μg mL−1 of HMSMs or UC-HMSMs (Figure 5B). RT-PCR analyses also showed that the expressions of apoptotic markers, such as antiapoptotic (BCL-XL) and proapoptotic (BAX), were not significantly different among the groups (Figure 5C). Considering that the previously reported silicabased core−shell structure containing UC oil showed negligible cytotoxicity against 3T3 fibroblasts only for concentrations below 10 μg mL−1,39 these results clearly reveal that the HMSMs and UCHMSMs are highly biocompatible, and can therefore be employed as TTA-UC carriers for cell-mediated TTA-UC systems with hMSCs. When the hMSCs treated with UC-HMSMs (denoted as “UChMSCs”) were washed with phosphate-buffered saline (PBS) and then irradiated with a 635 nm laser, the upconverted blue emission was clearly visible to the naked eye (Figure 5D,E). The strong binding of the UC-HMSMs on the surface of hMSCs was also supported by bright-field images showing that the UC-HMSMs were mainly localized on the surface of hMSC (black arrows, Figure S22A). The uptake of UC-HMSMs into the hMSCs was not observed mainly due to the former’s large size. However, although the detailed molecular and chemical mechanisms were not investigated, the UC-HMSMs were clearly attached on the cellular membrane with strong adhesion even after seven times of thorough washing with PBS. Furthermore, no morphological differences, such as round or floating cells indicative of cell death, were observed when compared to the NT group (Figure S22B). Further evidence of the high binding affinity between UCHMSMs and hMSCs was obtained from the dispersion of UChMSCs. When UC-hMSCs were resuspended in PBS and stored in a tube, a greenish pellet was precipitated at the bottom of the tube within 10 min (Figure 5F,G). When the tip of the tube was irradiated with the 635 nm laser, upconverted blue emission was clearly visible to the naked eye (Figure 5H), while the supernatant showed no UC emission under equivalent excitation (Figure 5I). Considering that the pristine UC-HMSMs can maintain stable water suspension for more than a day, these results support that the UC-HMSMs are tightly bound on the surface of hMSCs. The particle counts evaluated from the bright-field images (average of 100 tiles) also reveal that only an average of one particle/tile was found in the supernatant of the tube, which is far less than that of the initial UC-HMSMs concentration (13 particles/tile, Figure S23). To further verify that the upconverted blue emission originated from the UC-HMSMs, UC-hMSCs were visualized by CLSM. A strong upconverted blue emission was clearly detected when the culture was irradiated with the 640 nm laser and monitored in the 450−550 nm fluorescence channel (Figure S24B). An overlay of the bright-field and fluorescence channel images (Figures S24A and 5J) also confirms that the UC signal originated from the UC-HMSMs bound on the hMSCs. These results clearly indicate that the UC-HMSMs have high binding affinities for hMSCs, and therefore provide a fair applicability of our TTA-UC system to new anti-Stokes-based biophotonic applications. Further studies that address the specificities of UC-hMSCs for targeting tumor cells and their applications to low-power in vivo imaging are currently underway.

emission from the core of HMSMs was not observable when washed with ethanol, indicating that the encapsulated UC oil was completely removed from the HMSMs. After refilling with the UC oil containing PdTPBP and BPEA, the upconverted green emission was clearly verified through the 450−600 nm fluorescence channel (Figures 4G and S19), which corresponds to the upconverted emission spectra measured with a 635 nm laser (Figure S20). These results therefore support that the HMSMs can be effectively used as recyclable vehicles for TTA-UC, which can only be achieved based on the current postencapsulation strategy. 3.4. In Vitro TTA-UC Experiments. Bioimaging based on antiStokes emissions is one of the most significant upconversion application areas, due to its distinct photonic characteristics, such as ultra-high S/N ratios with negligible autofluorescence.34−36 To demonstrate an anti-Stokes emission-based biophotonic application of our UC-HMSMs, we describe a proof-of-concept in vitro cellmediated TTA-UC system by incorporating the UC-HMSMs onto tumor-tropic cells; these cells have been used as carriers that deliver materials specifically designed for anticancer therapy.37 In particular, among various tumor-tropic cell types, human mesenchymal stem cells (hMSCs) were selected for our experiments, due to their convenient isolation, expansion, minimal immunogenicities, and immunosuppressive properties that are required for cell transplantation.38 The schematic illustration for in vitro experiments of the cell-mediated TTA-UC system is depicted in Figure S21. We hypothesized that the UC-HMSMs developed in this study would be actively bound on the surface of hMSCs without significant cytotoxicity, thereby facilitating upconverted blue emission from the cell cultures when irradiated with the 635 nm laser. Prior to the TTAUC test, the particle concentration-dependent cytotoxicity of HMSMs and UC-HMSMs against hMSCs was first investigated (Figure 5A). Several works have reported the fabrication of silica-based UC

Figure 5. Cytotoxicity of HMSMs and UC-HMSMs evaluated by determining the viabilities of hMSCs using: (A) the CCK-8 assay after culturing for 24 h with various particle concentrations, and (B) the FDA−EB assay that stains live cells (green) and dead cells (red). (C) RT-PCR analyses of antiapoptotic (BCL-XL) and proapoptotic (BAX) genes expressed by hMSCs after treatment with HMSMs and UC-HMSMs separately. Digital images of hMSC culture after treatment with 200 μg mL−1 of UC-HMSMs, and then washing with PBS (D) under white light and (E) 635 nm laser excitation. Digital images of UC-hMSCs resuspension in PBS: (F) initial, (G) 10 min later, and with 635 nm laser excitation on (H) the pellet and (I) supernatant. (J) CLSM images of hMSCs under 640 nm excitation. The image is a merge of bright-field and fluorescence channel (450− 550 nm). Inset in (D) shows the scheme of UC-hMSC. Scale bars in (B) and (J) represent 50 and 20 μm, respectively.

4. CONCLUSIONS In summary, we developed new vehicles for aqueous phase photon upconversion using a post-encapsulation strategy, with HMSMs fabricated by a surfactant-assisted Stöber method, and a subsequent self-transformation approach. The prepared HMSMs possess tunable diameters, large interior cavities, H


Research Article


TTET, triplet−triplet energy transfer TEOS, tetraethyl orthosilicate CTAB, hexadecyltrimethylammonium bromide PdTPBP, palladium(II) meso-tetraphenyltetrabenzoporphyrin MSM, mesoporous silica microsphere RT, room temperature YMSM, yolk−shell structured magnetic silica microcapsule EDX, energy-dispersive X-ray BET, Brunauer−Emmett−Teller FDA, fluorescein diacetate EB, ethidium bromide RT-PCR, reverse transcriptase polymerase chain reaction PCR, polymerase chain reaction DIC, differential interference contrast BPEA, bis(phenylethynyl)anthracene PBS, phosphate-buffered saline

and ordered radial mesochannels that favor the controlled encapsulation of guest molecules, such as sensitizer and acceptor chromophores. The UC oil is readily encapsulated at high loadings into the HMSM through their highly accessible mesochannels, which was confirmed by the intense upconverted blue emission when irradiated with ultralow-power red light (23.3 mW cm−2). Together with the numerous previously reported advantages of silica nanoparticles, such as easy surface functionalization and excellent biocompatibility, the distinct advantages of UC-HMSMs were mainly exploited in the current work by demonstrating the adaptive inclusion of metal nanoparticles and the controlled encapsulation of UCchromophores. The synthetic flexibility and modifiability of our new TTA-UC system are important factors toward realizing economical and practical applications in biomedicine and environmental areas. We also successfully demonstrated an in vitro cell-mediated TTA-UC system by incorporating our UC-HMSMs on the surface of hMSCs, which facilitated the generation of upconverted blue emission from living cells when excited at 635 nm and thus showed great promise as an ideal host system for tumor-targeted low-power bioimaging. To the best of our knowledge, this study is the first to design biocompatible TTA-UC vehicles with a post-encapsulation strategy and diverse functionalities, thereby establishing a new and general platform to achieve efficient aqueous phase TTAUC for previously unexplored multifunctional applications.

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(1) Fischer, S.; Goldschmidt, J. C.; Löper, P.; Bauer, G. H.; Brüggemann, R.; Krämer, K.; Biner, D.; Hermle, M.; Glunz, S. W. Enhancement of Silicon Solar Cell Efficiency by Upconversion: Optical and Electrical Characterization. J. Appl. Phys. 2010, 108, No. 044912. (2) Hill, S. P.; Hanson, K. Harnessing Molecular Photon Upconversion in a Solar Cell at Sub-Solar Irradiance: Role of the Redox Mediator. J. Am. Chem. Soc. 2017, 139, 10988−10991. (3) Li, C.; Koenigsmann, C.; Deng, F.; Hagstrom, A.; Schmuttenmaer, C. A.; Kim, J. H. Photocurrent Enhancement from Solid-State Triplet−Triplet Annihilation Upconversion of LowIntensity, Low-Energy Photons. ACS Photonics 2016, 3, 784−790. (4) Kim, J. H.; Kim, J. H. Encapsulated Triplet−Triplet Annihilation-Based Upconversion in the Aqueous Phase for SubBand-Gap Semiconductor Photocatalysis. J. Am. Chem. Soc. 2012, 134, 17478−17481. (5) Huang, L.; Zhao, Y.; Zhang, H.; Huang, K.; Yang, J.; Han, G. Expanding Anti-Stokes Shifting in Triplet−Triplet Annihilation Upconversion for In Vivo Anticancer Prodrug Activation. Angew. Chem., Int. Ed. 2017, 56, 14400−14404. (6) Park, J.; Xu, M.; Li, F.; Zhou, H. C. 3D Long-Range Triplet Migration in a Water-Stable Metal−Organic Framework for Upconversion-Based Ultralow-Power In Vivo Imaging. J. Am. Chem. Soc. 2018, 140, 5493−5499. (7) Askes, S. H.; Mora, N. L.; Harkes, R.; Koning, R. I.; Koster, B.; Schmidt, T.; Kros, A.; Bonnet, S. Imaging the Lipid Bilayer of Giant Unilamellar Vesicles Using Red-to-Blue Light Upconversion. Chem. Commun. 2015, 51, 9137−9140. (8) Askes, S. H.; Pomp, W.; Hopkins, S. L.; Kros, A.; Wu, S.; Schmidt, T.; Bonnet, S. Imaging Upconverting Polymersomes in Cancer Cells: Biocompatible Antioxidants Brighten Triplet−Triplet Annihilation Upconversion. Small 2016, 12, 5579−5590. (9) Singh-Rachford, T. N.; Castellano, F. N. Photon Upconversion Based on Sensitized Triplet−Triplet Annihilation. Coord. Chem. Rev. 2010, 254, 2560−2573. (10) Jiang, X.; Guo, X.; Peng, J.; Zhao, D.; Ma, Y. Triplet−Triplet Annihilation Photon Upconversion in Polymer Thin Film: Sensitizer Design. ACS Appl. Mater. Interfaces 2016, 8, 11441−11449. (11) Monguzzi, A.; Tubino, R.; Meinardi, F. Upconversion-Induced Delayed Fluorescence in Multicomponent Organic Systems: Role of Dexter Energy Transfer. Phys. Rev. B 2008, 77, No. 155122. (12) Liu, Q.; Xu, M.; Yang, T.; Tian, B.; Zhang, X.; Li, F. Highly Photostable Near-IR-Excitation Upconversion Nanocapsules Based on Triplet−Triplet Annihilation for In Vivo Bioimaging Application. ACS Appl. Mater. Interfaces 2018, 10, 9883−9888. (13) Wohnhaas, C.; Mailänder, V.; Dröge, M.; Filatov, M. A.; Busko, D.; Avlasevich, Y.; Baluschev, S.; Miteva, T.; Landfester, K.; Turshatov, A. Triplet−Triplet Annihilation Upconversion Based

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.9b06620. Experimental results including characterization of HMSMs/YMSMs, and TTA-UC characteristics of UCHMSMs/YMSMs (PDF). Magnetic responsivities of the UC-YMSMs (MP4)

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REFERENCES

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (S.H.B.). *E-mail: [email protected] (J.-H.K.). ORCID

Nobuhiro Yanai: 0000-0003-0297-6544 Nobuo Kimizuka: 0000-0001-8527-151X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF2018R1D1A3B07049650). This work was also supported by a grant from a Korea Health Technology R&D Project (grant HI17C1728).

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ABBREVIATIONS HMSM, hollow mesoporous silica microcapsule TTA-UC, triplet−triplet annihilation upconversion UC-HMSM, upconverting oil-laden HMSM hMSC, human mesenchymal stem cell UC, upconversion TTA, triplet−triplet annihilation I


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Upconverting Oil-Laden Hollow Mesoporous Silica Microcapsules for

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