Mussel-Inspired Polydopamine-Coated Lanthanide Nanoparticles for

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Mussel-Inspired Polydopamine-Coated Lanthanide Nanoparticles for NIR-II/CT Dual Imaging and Photothermal Therapy Yu Dai,† Dongpeng Yang,† Danping Yu,‡ Cong Cao,† Qiuhong Wang,† Songhai Xie,† Liang Shen,‡ Wei Feng,*,† and Fuyou Li*,† †

Department of Chemistry, Fudan University, Shanghai 20043, People’s Republic of China School of Chemistry and Chemical Engineering, Jiangxi Engineering Laboratory of Waterborne Coating, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi 330013, People’s Republic of China

‡

S Supporting Information *

ABSTRACT: Nanomedicine has attracted substantial attention for the accurate diagnosis or treatment of carcinoma in recent years. Nd3+-doped lanthanide nanophosphor-based near-infrared-II (NIR-II) optical imaging is widely used for deep penetration tissue imaging while X-ray computed tomography (CT) is well-suited for in vivo imaging. Polymer-coated lanthanide nanophosphors are increasingly used in both diagnostics and therapies for tumor in vivo. However, the biocompatibility of nanocomposites and the efficiency of tumor ablation should be taken into consideration when constructing a nanotheranostic probe. In this article, we have fabricated polydopamine (PDA)-coated NaYF4:Nd3+@NaLuF4 nanocomposites using the reverse microemulsion approach. The thickness of the PDA shell can be precisely modulated from ∼1.5 to ∼18 nm, endowing the obtained NaYF4:Nd3+@ NaLuF4@PDA with an excellent colloidal stability and considerable biocompatibility. The photothermal conversion efficiency of the resultant nanocomposites was optimized and maximized by the increase of the PDA shell thickness. Because of the remarkable photothermal conversion efficiency, the mice xenograft tumors were completely eradicated after NIR irradiation. Given the considerable photoluminescence and X-ray attenuation efficiency, the performance of NaYF4:Nd3+@NaLuF4@PDA for NIR-II optical imaging and X-ray CT dual imaging of the tumor in vivo was evaluated. All of the results above highlight the great potential of PDA-based NaYF4:Nd3+@NaLuF4 nanocomposites as a novel multifunctional nanotheranostic agent. KEYWORDS: lanthanide, polydopamine, near-infrared-II, X-ray computed tomography, photothermal therapy

1. INTRODUCTION Photothermal therapy (PTT), as a noninvasive and potentially efficient cancer treatment, has recently drawn increasing interest.1−3 Tremendous efforts have been devoted to studies of photothermal agents on the nanometer scale, including noble metal nanoparticles (NPs),4−6 carbon nanomaterials,7,8 semiconductor nanocrystals,9,10 and some organic polymers,11−14 which exhibit high absorbance in the near-infrared (NIR) optical window (700−900 nm). However, the low biocompatibility and long-term toxicity of these inorganic NPs remarkably limit their potential use in future clinical translations.15 On the other hand, single PTT-based nanocomposites cannot meet the requirement of the development of theranostics. Thus, it is extremely urgent to fabricate a versatile nanosystem with high biocompatibility, which is composed of the multimodal imaging function to guide PTT toward tumors.16−21 Lanthanide NPs provide rich optical properties originating from the unique 4f electronic structure of the lanthanide elements.22−24 The large atomic number also endows lanthanide elements with a large X-ray attenuation for the © 2017 American Chemical Society

potential application as a computed tomography (CT) contrast probe.25−27 In particular, Nd3+-doped lanthanide nanophosphors have shown great potential for bioimaging, attributed to their efficient luminescent emission in the NIR-II region.28−31 It should be noted that any imaging modality technology has its own intrinsic advantages and disadvantages. For instance, photoluminescence imaging provides the highest spatial resolution; however, it suffers from poor anatomical and physiological details in vivo. Thus, combining X-ray CT with the optical imaging technique can fully take the advantages of each and avoid the weaknesses of both, which is more preferable for precision diagnosis.32,33 Polydopamine (PDA) coating has become an alternative to traditional polymer coating because of the following advantages of melanin-inspired PDA NPs: (1) strong NIR absorbance;11,12,34 (2) good biocompatibility and biodegradability;34−37 (3) excellent hydrophilicity;34,38,39 (4) feasibility of functional group modificaReceived: May 6, 2017 Accepted: July 20, 2017 Published: July 20, 2017 26674

DOI: 10.1021/acsami.7b06109 ACS Appl. Mater. Interfaces 2017, 9, 26674−26683

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ACS Applied Materials & Interfaces tion;34,40,41 and (5) polymerization on any object surface.34,42,43 It is of great importance to mention that coating Er3+-doped upconversion nanoparticles (UCNPs) with a PDA shell was fabricated by the following two strategies: (1) reverse microemulsion which directly coats PDA onto the hydrophobic UCNPs44 and (2) hydrophobic oleic acid (OA)-capped UCNPs are transferred ligand-free by NOBF4 before polymerization of dopamine molecules under Tris-HCl (pH 8.5) aqueous conditions.45 These multifunctional UNCP@PDA nanocomposites have been used for multimodal imagingguided PTT. To the best of our knowledge, there were no reports about the synthesis and application of NaYF4:Nd3+@ NaLuF4@PDA in terms of NIR-II optical/X-ray CT dualmodal imaging and PTT in vivo. Herein, we have strategically designed and synthesized versatile NaYF4:Nd3+@NaLuF4@PDA nanocomposites and then applied them as a theranostic platform that leveraged optics/CT to enable spatial- and temporal-specific imaging and PTT toward the tumor. NaYF4:Nd3+@NaLuF4 nanophosphors show an enhanced NIR photoluminescence and excellent X-ray attenuation. The PDA shell coating conferred the NPs with remarkable photothermal conversion capability as well as good biocompatibility. The PDA shell thickness could be modulated from ∼1.5 to ∼18 nm. When the thickness of the PDA shell reached to ∼18 nm, the nanocomposites had maximum photothermal conversion efficiency. Such a strategy to prepare a typical core−shell−shell nanostructure of NaYF4:Nd3+@ NaLuF4@PDA provides a simple but powerful imaging and a PTT probe for precision cancer treatment.

obtained NP@PDA nanocomposites were precipitated with ethanol, collected by centrifugation (14 000 rpm for 10 min), and washed with ethanol and water three times. Finally, the NP@PDA nanocomposites were ready to be dispersed in 10 mL of water for further use. The PDA shell thickness was modulated via different amounts of dopamine hydrochloride added into the reverse emulsion system (5 mg for ∼1.5 nm, 10 mg for ∼3 nm, 20 mg for ∼6 nm, 40 mg for ∼12 nm, and 80 mg for ∼18 nm). 2.3. Material Characterization. The morphology of NaYF4:Nd3+ NPs, NaYF4:Nd3+@NaLuF4 NPs, and NaYF4:Nd3+@NaLuF4@PDA nanocomposites was characterized by using a transmission electron microscope (Tecnai G2 20 TWIN, FEI) at an accelerating voltage of 200 kV. Power X-ray diffraction (XRD) measurements were evaluated on diffraction (X’Pert PRO, PANalytical) at a scanning rate of 5° min−1 in the 2θ range of 10°−90°. Fourier transform infrared (FTIR) analysis was performed on an FTIR spectroscope (Nicolet 6700, Thermo Fisher) using KBr-pressed plates. Dynamic light scattering (DLS) was introduced into a nanoparticle size analyzer (ZS-90, Marven) to measure the hydrodynamic diameter of NP@PDAn. Thermogravimetric analysis (TGA) was conducted on a thermogravimetric analyzer (TGA 1, METTLER TOLEDO) under an air atmosphere with a heating rate at 20 °C min−1. An ultraviolet−visible (UV−vis)−NIR spectrum was recorded with an absorption spectrometer (Lambda750, PerkinElmer) at room temperature. Photoluminescence emission spectra were recorded on a luminescence spectrometer (FLS920, Edinburgh) with an external continuous-wave (CW) 808 nm laser. Different concentrations of NP@PDA18 aqueous solution and the control commercial X-ray imaging agents, iodixanol injection solution, were monitored by micro-CT (SkyScan 1176, Bruker) with an Al 0.5 mm filter and an X-ray voltage of 50 kV; the Hounsfield units (HU) value was calculated via commercial software provided by Bruker. 2.4. Photothermal Performance Measurement. For comparing the photothermal conversion performance of NP@PDAn, 1 mL aqueous dispersion of NP@PDAn nanocomposites (400 μg mL−1) was introduced in a quart cuvette and irradiated with an 808 nm laser at 8 W cm−2 for 10 min and cooled down for 20 min; the pattern of temperature change was monitored by an infrared thermal camera (E40, FLIR) and quantified by the corresponding software. The thermal conversion efficiency was calculated as previously reported by Roper46 using the following eq 1

2. MATERIALS AND EXPERIMENTS 2.1. Materials. All chemicals were of analytical grade and used without further purification. OA (90%), 1-octadecene (ODE, 90%), IGEPAL CO-520, dopamine hydrochloride, and 3-4,5-dimethylthiazol2-yl-2,5-diphenylte-trazolium bromide (MTT) were obtained from Sigma-Aldrich. Ammonium fluoride (NH4F), sodium hydroxide (NaOH), hydrochloric acid (HCl), methanol, ethanol, and cyclohexane were obtained from Sinopharm Chemical Reagent Co., Ltd. Dulbecco’s modified Eagle medium (DMEM), phosphate-buffered saline (PBS), and fetal bovine serum (FBS) were obtained from Invitrogen Gibco. VISIPAQUE injection solution was obtained from GE Healthcare. The rare-earth oxides RE2O3 (99.999%) (RE = Y, Lu, and Nd) were purchased from Shanghai Yuelong New Materials Co., Ltd. RECl3 was prepared by dissolving the corresponding rare-earth oxides in hydrochloric acid at 110 °C. 2.2. Synthesis of NP@PDA Nanocomposites. NaYF4:Nd3+ core NPs were prepared with the solvent-thermal method.33 Typically, 1 mmol RECl3 (RE = Y, Nd) with a molar ratio of 97:3 was mixed with 6 mL of OA and 15 mL of ODE. The mixture was heated to 160 °C for 30 min to dissolve RECl3 and then cooled to 60 °C. Methanol solution (10 mL) containing NH4F (4 mmol) and NaOH (2.5 mmol) was added to the mixture dropwise. After being stirred at 160 °C to remove methanol, the solution was quickly heated to 300 °C and maintained at this temperature under an argon atmosphere for 1 h. After cooling down to room temperature, the NPs were precipitated by 10 mL of ethanol and washed with ethanol/cyclohexane three times; OA-stabilized NaYF4:Nd3+ NPs were ready to be dispersed in 10 mL of cyclohexane. The NaLuF4 inert shell was deposited on the NaYF4:Nd3+ core via a similar step. The NP@PDAn nanocomposites were prepared via the reverse microemulsion method. Typically, 30 mg of OA-NaYF4:Nd3+@NaLuF4 NPs and 1 g of IGEPAL CO-520 were dissolved in 10 mL of cyclohexane and stirred vigorously for 30 min; 0.1 mL of ammonium hydroxide (28%) was carefully added into the solution, followed by shaking at 120 rpm for 1 h, and then 40 mg of dopamine hydrochloride was added into the solution during the ultrasonic treatment. After shaking for 24 h at room temperature, the

η=

hAΔTmax − Q s I(1 − 10−Aλ)

(1)

where h is the heat transfer coefficient, A is the surface area of the container, ΔTmax is the maximum temperature change of the NP@ PDAn nanocomposite solution from the steady-state temperature, Qs is the heat associated with the light absorbance of the solvent, I is the laser power, Aλ is the absorbance of the NP@PDAn nanocomposite solution at 808 nm, and η is the photothermal conversion efficiency. The value of hA is calculated using eq 2

hA =

∑ miCp , i τs

(2)

where τs is the sample system time constant and mi and Cp,i are the mass and heat capacity of the solvent, respectively. The value of τs is calculated by the pattern of the cooling curve (Figure S1, Supporting Information) and introduced by eq 3 τs = −

t ln θ

(3)

According to eqs 1−3, the η value of NP@PDAn nanocomposites with the PDA shell thickness at ∼1.5, ∼3, ∼6, ∼12, and ∼18 nm can be calculated. 2.5. Photothermal Ablation of Cancer Cells in Vitro. HeLa cells were cultured in DMEM supplemented with 10% FBS and 1% penicillin−streptomycin at 37 °C in an atmosphere of 5% CO2 and 95% air. HeLa cells were seeded into a 96-well plate at 5 × 104 per 26675


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ACS Applied Materials & Interfaces well; NP@PDA20 nanocomposites were diluted in DMEM at a certain concentration and then added to the wells. Subsequently, the HeLa cells were incubated for 2 h, followed by irradiation with an 808 nm laser at a certain power density. The cells were incubated for another 24 h, MTT (20 μL, 5 mg mL−1) was added to each well, and then the plate was incubated for an additional 4 h at 37 °C. DMSO was added to the wells before the suspension was removed. The optical density OD 570 value of each well was recorded by a microplate reader (ELx800, BioTek) with background subtraction at 690 nm. The HeLa cells were incubated with NP@PDA18 at a concentration of 400 μg mL−1 for 2 h and then irradiated with different laser power densities (0, 2, 4, and 8 W cm−2) for 10 min. After treatment, the cells were costained with calcein AM and propidium iodide (PI) and imaged by confocal microscopy (FV1000, Olympus). The fluorescein isothiocyanate (FITC)-Annexin V apoptosis detection assay was performed to investigate the pathway of photothermal-induced death. After the corresponding treatment, HeLa cells were collected and stained with FITC-Annexin V and PI and analyzed by flow cytometry (Gallios, Beckman Coulter). 2.6. Tumor Imaging and Phototherapy in Vivo. BALB/c nude mice, 4 weeks old, were purchased from the Shanghai SLAC Laboratory. All animal experiments were under protocol approved by the Animal Experiment and Care Committee of the Fudan University. HeLa cells (1 × 106) suspended in PBS were inoculated subcutaneously in a flask of male nude mice. The mice were used for further imaging or PTT experiments when the tumor had grown to 0.3−0.5 cm in diameter. A modified in vivo imaging system was employed to image the NP@PDA18 nanocomposite-treated mice using an 808 nm optical fiber-coupled laser as the exciting source. An 890 nm long-pass emission filter was used to prevent the interference of exciting light on the charge-coupled device (CCD) camera. The CT images were taken by SkyScan 1176 in vivo microtomography and reconstructed by the corresponding software provided by Bruker. The mice bearing HeLa tumor cells were randomly allocated into four groups. During the laser irradiation, infrared thermal images were captured using an infrared thermal camera. After PTT, the survival rate was monitored, and the tumor size was carefully recorded. To examine the histological change of the tumors, the tumor-bearing mice were killed before and after PTT, and the tumors were removed and stained with hematoxylin and eosin for histopathology analysis.

Figure 1. TEM images of (a) NaYF4:Nd3+ nanocrystals, (b) NaYF 4 :Nd 3+ @NaLuF 4 nanocrystals, and (c,d) NaYF 4 :Nd 3+ @ NaLuF4@PDA nanocomposites with different magnifications.

nanospheres (Figure 1b) are of ∼23 and 30 nm in diameters, respectively. The inert shell can be identified in the scanning transmission electron microscopy−high-angle annular dark field (STEM−HAADF) image (Figure S2a, Supporting Information). XRD patterns of these NPs are well-indexed and assigned to the typical hexagonal phase structure of pure NaYF4 (JCPDS no. 16-0334) (Figure S3, Supporting Information). As reported previously,28 under excitation from a CW 808 nm laser, NaYF4:Nd3+@NaLuF4 exhibits two characteristic photoluminescence emission bands centered at ∼900 and ∼1060 nm originating from 4F3/2 → 4I9/2 and 4F3/2 → 4I13/2 transitions of Nd3+, respectively. The photoluminescence intensity is significantly improved after NaLuF4 inert shell deposition (Figure S4). The PDA outer shell was deposited via the waterin-oil reverse microemulsion method, as reported recently.44,48 In the presence of ammonia water, the PDA shell grows on the surface of NaYF4:Nd3+@NaLuF4 nanocrystals where the water droplets rendered a microreactor for the self-polymerization of dopamine under ambient conditions.49 The TEM and STEM− HAADF images of the typical core−shell structure of the NaYF4:Nd3+@NaLuF4@PDA nanocomposites are shown in Figures 2c,d, S5, and S2b, where an ∼10 nm uniform PDA outer shell is consistently and uniformly deposited on the NaYF4:Nd3+@NaLuF4 nanocrystals without a significant multicore coating and core-free PDA particles. After the PDA shell coating, the XRD patterns of NaYF4:Nd3+@NaLuF4@PDA nanocomposites are similar to those of NaYF4:Nd3+@NaLuF4 NPs, indicating that the PDA coating cannot change the crystalline phase of NaYF4:Nd3+@NaLuF4 (Figure S3, Supporting Information), which is also confirmed by the highresolution transmission electron microscopy (HRTEM) images (Figure S6, Supporting Information). The FTIR spectroscopy result is plotted in Figure S7, Supporting Information, which confirms the chemical characteristic peaks of OA and PDA. The obtained uniform monodisperse PDA shell-coated NPs are described here as NP@PDA. Because of substantive hydroxyl and amine groups on the surface, the NP@PDA nanocomposites exhibit excellent dispersity in polar solvents such as DMEM, FBS, PBS, saline, water, and dimethylsulfoxide (DMSO), forming a clear brown colloidal solution and is stable in suspension for as long as 2 months at room temperature (Figure S8, Supporting Information).

3. RESULTS AND DISCUSSION 3.1. Synthesis and Characterization of NaYF4:Nd3+@ NaLuF4@PDA. The nanocomposites consist of an NaYF4:Nd3+ core, an NaLuF4 inert shell, and a PDA outer shell, as illustrated in Scheme 1. The NaYF4 nanocrystals doped with 3 mol % Nd3+ were synthesized via the typical solvent-thermal method.47 As shown in the transmission electron microscopy (TEM) images, the obtained NaYF4:Nd3+ (Figure 1a) and NaYF4:Nd3+@NaLuF4 Scheme 1. Schematic Illustrations of NaYF4:Nd3+@ NaLuF4@PDA as NIR-II Nanophosphors, CT Contrast Agent, and Simultaneous PTT Agent on Xenograft Tumors

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nanocomposites was further conducted. As shown in Figure 3b, the increasing weight loss of [email protected] (15.93%), NP@ PDA3 (27.72%), NP@PDA6 (37.07%), NP@PDA12 (58.8%), and NP@PDA18 (71.75%) can be ascribed to the increase of the PDA shell thickness. 3.3. NIR-II and CT Imaging in Vivo. To assess the photoluminescence emission of the NP@PDAn nanocomposites under excitation of CW 808 nm, NIR-II fluorescence spectra of NP@PDAn aqueous solution were recorded. The emission spectra illustrate that the fluorescence emission at 1060 nm of NP@PDAn is slightly weaker as the PDA shell thickness increases (Figure 4a). The photoluminescence comparison between NaYF 4 :Nd 3+ @NaLuF 4 @PDA and NaYF4:Nd3+@NaLuF4@SiO2 with the same shell thickness was introduced; it was found that the PDA coating exactly quenched the NIR-II emission at 1060 nm (Figure S9, Supporting Information), which can be probably explained by the self-absorption11 and/or resonance energy transfer manner of PDA.50 Even though the PDA shell can prevent the intrinsic NIR-II photoluminescence emission of Nd3+-doped lanthanide nanophosphors, we choose NP@PDA18 as the nanoprobe for optical bioimaging because NP@PDA18 has the greatest photothermal conversion efficiency, as discussed later. We performed an in vivo NIR-II imaging of the HeLa tumorbearing nude mice before/after intratumoral injection of these NPs dispersed in saline (100 μL, 3 mg mL−1 per animal). The luminescent NIR-II signal was captured upon irradiation by a CW 808 nm laser with a power density of 1 W cm−2. Figure 4b,c points out that the intrinsic NIR-II luminescence of NP@ PDA18 nanocomposites is clearly observed in tumor sites. The minimal autofluorescence and low absorbance and scattering of NIR-II emission afford a high signal/noise ratio and maximal penetration depth,51,52 which facilitates the NIR-II optical imaging of the tumor. To obtain further physiological and anatomical details of the mice, X-ray CT was applied to improve the efficiency of optical imaging. X-ray CT imaging has the ability to provide an excellent spatial resolution and depth for imaging in vivo. The atomic number (Z) of the CT agent determines the X-ray attenuation coefficient. Theoretically, the lutetium (Z = 71)based NP@PDA18 nanocomposites are superior to the iodine (Z = 53)-based commercial X-ray imaging agent, iodixanol, in VISIPAQUE injection solution, in terms of X-ray CT imaging.53,54 To evaluate the X-ray imaging effect of the NP@PDA18 nanocomposites, different concentrations of NP@ PDA18 nanocomposites were monitored by X-ray CT to determine the HU value, using iodixanol injection solution as the control. Figure 5a illustrates the CT imaging of both NP@

Figure 2. TEM images of (a) [email protected] nanocomposites, (b) NP@ PDA3 nanocomposites, (c) NP@PDA6 nanocomposites, (d) NP@ PDA12 nanocomposites, and (e) NP@PDA18 nanocomposites; (f) relationship between the PDA shell thickness and the amount of monomer dopamine hydrochloride; data are presented as mean ± SD.

3.2. Modulation of PDA Shell Thickness. The control synthesis of NP@PDA with tunable shell thickness is challenging but critical for further applications. Given that the photothermal conversion capability of PDA is associated with absorption in the NIR region,11 it was hypothesized that the photothermal performance of NP@PDA might be subject to the PDA shell thickness. TEM images illustrate the evolution of NP@PDA with different shell thicknesses (Figure 2a−e). The obtained nanocomposites with different PDA shell thicknesses are described here as [email protected], NP@PDA3, NP@PDA6, NP@PDA12, and NP@PDA18 (footnote means thickness of the PDA shell in nanometers). The shell thickness was tunable through varying the amount of dopamine hydrochloride in the reverse microemulsion mixture during the coating process. Their relationship is plotted in Figure 2f. DLS analysis (Figure 3a) indicates that the hydrodynamic diameters of NP@PDAn are ∼30, ∼33, ∼37, ∼50, and ∼79 nm. To quantitatively evaluate the PDA shell coating on the surface of the NaYF4:Nd3+@NaLuF4 NPs, TGA of the NP@PDAn

Figure 3. (a) Size distribution of NP@PDAn nanocomposites and (b) TGA curve of NP@PDAn nanocomposites. 26677


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Figure 4. (a) NIR-II emission spectra of NP@PDAn nanocomposites, λex = 808 nm; in vivo and in situ NIR-II imaging of nude mice bearing HeLa tumors (b) before and (c) after intratumoral injection of 100 μL of NP@PDA18 solution (3 mg mL−1); λex = 808 nm and λem = 1060 nm.

Figure 5. (a) X-ray CT images and (b) HU values of NP@PDA18 nanocomposites and iodixanol aqueous solution with different concentrations; Xray CT images of the HeLa tumor-bearing nude mice (c) before and (d) after intratumoral injection of 100 μL of NP@PDA18 solution (3 mg mL−1).

nanocomposites (100 μL, 3 mg mL−1). These above-mentioned results demonstrate the successful construction of NIR-II plus CT imaging agent and the availability of NP@PDA 18 nanocomposites as an excellent bimodal probe for tumor imaging. 3.4. Photothermal Effect of NP@PDAn Nanocomposites. The absorbance intensity in the NIR region is a key factor to determine the photothermal conversion capability of the PTT agent. UV−vis−NIR absorbance spectra of NP@ PDAn nanocomposites are shown in Figure 6a. NP@PDAn nanocomposites have a broad absorbance band ranging from the UV to the NIR region. The absorbance of the NP@PDAn nanocomposites at 808 nm is positively related to the thickness

PDA18 and iodixanol aqueous solution in the range of 0−15 mg mL−1. As plotted in Figure 5b, the HU values increase linearly with the increase in the concentration of both NP@PDA18 nanocomposite aqueous solution and iodixanol injection solution. The slope of the HU value for the NP@PDA18 nanocomposites is about 45.23, which is much higher than that for iodixanol (20.37), demonstrating that NP@PDA18 nanocomposites are excellent X-ray contrast agents and have great potential in CT imaging in vivo. Then, HeLa tumorbearing nude mice were transferred to the micro-CT system to obtain the CT images, which are shown in Figure 5c,d; significant X-ray attenuation signals are highlighted within the tumor sites after the intratumoral injection of NP@PDA18 26678


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Figure 6. (a) UV−vis−NIR spectra of NP@PDAn aqueous solution. Inset: photograph of NP@PDAn aqueous solution; (b) photothermal response of NP@PDAn aqueous solution (400 μg mL−1) for 600 s with an NIR laser (808 nm, 8 W cm−2), and then the laser was shut off; (c) temperature variation curves of 1 mL of NP@PDA18 nanocomposite solution with different concentrations (0, 25, 50, 100, 200, 400, 600, 800, and 1000 μg mL−1) recorded under 808 nm laser irradiation with a power density of 8 W cm−2; and (d) temperature variation curves of 1 mL of NP@PDA18 nanocomposites solution (400 μg mL−1) recorded under 808 nm laser irradiation with different power densities (0, 0.5, 2, 3.5, 5, 6.5, 8, 9.5, and 11 W cm−2).

absorbance because of photobleaching55 and morphological change,11 respectively, after long irradiation exposure (Figure S10c,d, Supporting Information). To further evaluate the photothermal performance of NP@PDA18 nanocomposites, we recorded the temperature elevation of the NP@PDA18 nanocomposite solution with different concentrations under 808 nm laser irradiation at 8 W cm−2 for 600 s. As shown in Figure 6c, the rate of temperature elevation of the colloidal solution shows a typical concentration-dependent manner. By contrast, the temperature of pure water increased by only 3 °C. Similarly, the photothermal performance of NP@PDA18 nanocomposites depends on the power density of the 808 nm laser (Figure 6d). 3.5. Photothermal Therapy in Vitro. Before exploring the photothermal performance of NP@PDA18 nanocomposites in vitro, we evaluated the cytotoxicity of the NP@PDA18 nanocomposites by the standard MTT approach. The MTT results demonstrate that the NP@PDA18 nanocomposites do not exert any obvious suppressive effect on the proliferation of HeLa cells after incubation for 24 or 48 h even in relatively high concentrations up to 1000 μg mL−1 (Figure S11, Supporting Information), ensuring the biocompatibility of NP@PDA18 nanocomposites in vitro. Subsequently, we investigated the potential of NP@PDA18 as a PTT agent for cancer ablation. As shown in Figure 7a,b, the cell viability decreases gradually with increasing concentration of NP@PDA18 nanocomposites or laser power density, suggesting that HeLa cells are eliminated in a concentrationdependent and power density-dependent manner after PTT treatment. The result is also validated by confocal fluorescence images (Figure 7c) of calcein AM and PI costaining of HeLa cells. To make clear the cell death mechanism underlying PTT, HeLa cells were assigned into four groups: (i) negative control;

of the PDA shell. The absorbance at the NIR region of the NP@PDAn nanocomposites makes them highly promising as a PTT agent. To assess the photothermal performances of the NP@PDAn nanocomposites with different PDA shell thicknesses, the temperature variation curve of the NP@PDAn nanocomposites under 808 nm excitation was recorded by an infrared thermal camera. Figure 6b illustrates the increase in the rate of temperature elevation with an increase in the PDA shell thickness. The photothermal conversion efficiency (η) of a set of NP@PDAn nanocomposites with different PDA shell thicknesses of 1.5, 3, 6, 12, and 18 nm was calculated to be 24.76, 40.84, 46.86, 48.43, and 51.63%, respectively, indicating that η of NP@PDAn nanocomposites is tunable according to the thickness of the PDA shell. The η of NP@PDA3 is in proximity to the literature reported by the Zhou group;45 when the PDA shell thickness is ∼2.5 nm, η of UCNP@PDA nanocomposites is 40.6%. The η of NP@PDA18 is 51.63%, which is much higher than that of the conventional PTT agent such as gold nanorod (GNR) (21%) and Cu2−xSe (22%).9 Thus, it is obvious that NP@PDA18 nanocomposites are optimal candidates as a PTT agent and are selected for further experiments in vitro and in vivo. To demonstrate the photostability of NP@PDA18 nanocomposites, the solution of NP@PDA18 nanocomposites was exposed to 808 nm irradiation for 5 min, followed by cooling down for 5 min. As shown in Figure S10a, after seven cycles of laser on/off irradiation, no notable decrease of the temperature elevation is observed. Meanwhile, there is no significant absorbance and morphology change of NP@PDA18 nanocomposites at 808 nm before/after the NP@PDA18 aqueous solution was subjected to 808 nm laser with a power density at 8 W cm−2 for 2 h (Figure S10b, Supporting Information). By contrast, indocyanine green (ICG) and GNR lost their NIR 26679


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Figure 7. (a) Cell viability of HeLa cells treated with different concentrations of NP@PDA18 nanocomposites and laser irradiation (808 nm, 8 W cm−2, 10 min); (b) cell viability of HeLa cells incubated with NP@PDA18 nanocomposite solution (400 μg mL−1) and irradiated with different power densities for 10 min; (c) confocal images of calcein AM (green, live cells) and PI (red, dead cells) costained HeLa cells after irradiation at different power densities for 10 min. The scale bar is 100 μm in all images; (d) flow-cytometry-based apoptosis analysis of HeLa cells after corresponding treatment; and (e) photograph of HeLa colony formation after corresponding treatment.

3.6. Photothermal Therapy in Vivo. Motivated by the excellent PTT efficiency of NP@PDA18 nanocomposites in vitro, we evaluated the in vivo PTT efficiency of NP@PDA18 on HeLa tumor-bearing nude mice. First, the in vivo photothermal temperature elevation profiles of tumors (region 1) and adjacent normal tissues (region 2) were recorded by an infrared thermal camera (Figure 8a). It was found that the temperature of HeLa tumor tissues on mice after intratumoral injection of NP@PDA18 solution (100 μL, 3 mg mL−1) can rise rapidly under the 808 nm irradiation. The temperature increases from ∼30 to ∼70 °C within 5 min and remains steady at ∼75 °C within 10 min with an irradiation power density at 8 W cm−2, whereas the temperature of the saline injection tumor showed ∼20 °C increase within 10 min under the same irradiation conditions. NP@PDA18- or saline-injected mice exhibit only ∼4 °C elevation on tumor-adjacent tissues, suggesting that PTT has negligible effect on normal tissues around the tumor (Figure 8b), which is desirable in clinical applications. The tumor sizes were recorded 20 days after

(ii) irradiation alone; (iii) nanocomposites’ incubation alone, and (iv) PTT group. The Annexin-V/PI apoptosis assay was instantly carried out after the corresponding treatment. As plotted in Figure 7d, PTT treatment results in the death of 34.3% cells in a necrotic manner, which is proved by the cells costained with Annexin V-FITC and PI. By contrast, only irradiation or NP@PDA18 incubation has a negligible effect on cells compared with the negative control, which is also verified by typan blue staining results (Figure S12, Supporting Information). To evaluate the long period effect of photothermal treatment on the proliferation of cancer cells, the colony formation assay was performed, as shown in Figure 7e. After the corresponding treatment and 3 weeks of incubation, HeLa cells could not proliferate into a colony after PTT treatment. Meanwhile, in the other three groups, HeLa cells grew and then accumulated into a significant colony. These results suggest that NP@PDA18 nanocomposite-based PTT is sufficient to induce localized hyperthermia to ablate the cancer cells in vitro. 26680


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Figure 8. (a) Photothermal imaging of tumor-bearing mice with irradiation. Yellow circle: tumor tissues (region 1); red circle: adjacent normal tissues (region 2); (b) tumor tissues (region 1) & adjacent normal tissues (region 2) profiles of tumor-bearing mice recorded during the laser irradiation after intratumoral injection of NP@PDA18 nanocomposite solution (100 μL, 3 mg mL−1) or saline (100 μL); (c) photographs of tumor from different groups of mice at the end of PTT; (d) survival rates of four groups of mice (n = 6) as a function of time, posttreatment; and (e) H&E staining of tumor tissues harvested from mice with or without PTT. The scale bar is 100 μm.

hydrophilic shell of nature-inspired PDA for PTT. We investigated the effect of the PDA shell thickness on the photothermal conversion efficiency and found that when the PDA shell thickness reached to 20 nm, the photothermal conversion efficiency of the nanocomposites was as high as 51.63%. The core−shell−shell structure of the NP@PDA18 nanocomposites showed high biocompatibility, NIR-II/CT spatial- and temporal-specific tumor imaging, and outstanding photothermal conversion capability. Massive HeLa cells were observed to be eliminated in the necrotic pathway when the cells incubated with the NP@PDA18 nanocomposites were irradiated with the 808 nm laser. Using these nanocomposites as probes, we realized optical imaging in the NIR-II window and X-ray CT imaging in HeLa tumor-bearing mice after intratumoral injection. Moreover, NP@PDA18 nanocomposites showed a high photothermal therapeutic efficiency in ablation tumors. Overall, our work demonstrates a nanocomposite consisting of an inorganic NaYF4:Nd3+@NaLuF4 core and an organic PDA shell, in general, for application in cancer theranostics and nanomedicine.

different treatments (Figure 8c). It was found that after PTT, tumors are completely eliminated. By contrast, tumors receiving other control treatments including irradiation only or nanocomposites injection only do not show any suppression compared with the negative control. Then, we monitored the survival rate of mice to evaluate the PTT efficiency, as shown in Figure 8d. After PTT treatment, the mice are tumor-free and survive for more than 35 days, whereas the mice in the other three control groups die within 28 days. As shown in Figure 8e, hematoxylin and eosin (H&E) staining was introduced to exhibit the pathological change of tumor tissues after PTT, which displayed a typical necrotic phenomenon including nuclear damage, cell shrinkage, and loss of contact, which were well-consistent with the Annexin-V/PI apoptosis assay results shown in Figure 7d. The results above strongly indicate that PTT with NP@PDA18 nanocomposites is sufficient to induce hyperthermia and ablate tumor in vivo under NIR excitation. The biosafety of the nanocomposites is also evaluated. It was found that BALB/c mice after intravenous injection of NP@ PDA18 nanocomposites behaved normally without a noticeable decrease in the bodyweight (Figure S13, Supporting Information). The excretion route of the present NPs has probably been eliminated via the hepatic pathway.56 No appreciable sign of organ damage or inflammatory lesion was observed in the NP@PDA18 injection group compared with the saline injection group, as revealed by the H&E staining of major organ slices of these mice (Figure S14, Supporting Information), which further confirms the biosafety of the NP@PDA18 nanocomposites.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.7b06109. Additional TEM images, HRTEM images, HAADF− STEM images, FTIR spectra, XRD spectra of obtained NaYF4:Nd3+@NaLuF4 nanocrystals and NaYF4:Nd3+@ NaLuF4@PDA nanocomposites, cooling period versus negative natural logarithm of the driving force temperature, stability study, and biotoxicity in vitro and in vivo study of NaYF4:Nd3+@NaLuF4@PDA nanocomposites (PDF)

4. CONCLUSIONS In summary, we have designed and synthesized a three-layer core−shell−shell nanocomposite (NaYF4:Nd3+@NaLuF4@ PDA) composed of an inner core of Nd3+-doped NaYF4 nanophosphors, an inert layer of NaLuF4 for enhanced photoluminescence emission and CT imaging, and an outer 26681


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PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy. ACS Appl. Mater. Interfaces 2015, 7, 8176−8187. (15) Peynshaert, K.; Manshian, B. B.; Joris, F.; Braeckmans, K.; De Smedt, S. C.; Demeester, J.; Soenen, S. J. Exploiting Intrinsic Nanoparticle Toxicity: The Pros and Cons of Nanoparticle-Induced Autophagy in Biomedical Research. Chem. Rev. 2014, 114, 7581−7609. (16) Skeete, Z.; Cheng, H.; Crew, E.; Lin, L.; Zhao, W.; Joseph, P.; Shan, S.; Cronk, H.; Luo, J.; Li, Y.; Zhang, Q.; Zhong, C.-J. Design of Functional Nanoparticles and Assemblies for Theranostic Applications. ACS Appl. Mater. Interfaces 2014, 6, 21752−21768. (17) Pelaz, B.; Alexiou, C.; Alvarez-Puebla, R. A.; Alves, F.; Andrews, A. M.; Ashraf, S.; Balogh, L. P.; Ballerini, L.; Bestetti, A.; Brendel, C.; Bosi, S.; Carril, M.; Chan, W. C. W.; Chen, C.; Chen, X.; Chen, X.; Cheng, Z.; Cui, D.; Du, J.; Dullin, C.; Escudero, A.; Feliu, N.; Gao, M.; George, M.; Gogotsi, Y.; Grünweller, A.; Gu, Z.; Halas, N. J.; Hampp, N.; Hartmann, R. K.; Hersam, M. C.; Hunziker, P.; Jian, J.; Jiang, X.; Jungebluth, P.; Kadhiresan, P.; Kataoka, K.; Khademhosseini, A.; Kopeček, J.; Kotov, N. A.; Krug, H. F.; Lee, D. S.; Lehr, C.-M.; Leong, K. W.; Liang, X.-J.; Lim, M. L.; Liz-Marzán, L. M.; Ma, X.; Macchiarini, P.; Meng, H.; Möhwald, H.; Mulvaney, P.; Nel, A. E.; Nie, S.; Nordlander, P.; Okano, T.; Oliveira, J.; Park, T. H.; Penner, R. M.; Prato, M.; Puntes, V.; Rotello, V. M.; Samarakoon, A.; Schaak, R. E.; Shen, Y.; Sjöqvist, S.; Skirtach, A. G.; Soliman, M. G.; Stevens, M. M.; Sung, H.-W.; Tang, B. Z.; Tietze, R.; Udugama, B. N.; VanEpps, J. S.; Weil, T.; Weiss, P. S.; Willner, I.; Wu, Y.; Yang, L.; Yue, Z.; Zhang, Q.; Zhang, Q.; Zhang, X.-E.; Zhao, Y.; Zhou, X.; Parak, W. J. Diverse Applications of Nanomedicine. ACS Nano 2017, 11, 2313−2381. (18) Chen, G.; Roy, I.; Yang, C.; Prasad, P. N. Nanochemistry and Nanomedicine for Nanoparticle-Based Diagnostics and Therapy. Chem. Rev. 2016, 116, 2826−2885. (19) Shi, J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer Nanomedicine: Progress, Challenges and Opportunities. Nat. Rev. Cancer 2017, 17, 20−37. (20) Wang, D.; Liu, B.; Quan, Z.; Li, C.; Hou, Z.; Xing, B.; Lin, J. New Advances on the Marrying of Ucnps and Photothermal Agents for Imaging-Guided Diagnosis and the Therapy of Tumors. J. Mater. Chem. B 2017, 5, 2209−2230. (21) Chen, Q.; Wen, J.; Li, H.; Xu, Y.; Liu, F.; Sun, S. Recent Advances in Different Modal Imaging-Guided Photothermal Therapy. Biomaterials 2016, 106, 144−166. (22) Zhou, J.; Liu, Z.; Li, F. Upconversion Nanophosphors for SmallAnimal Imaging. Chem. Soc. Rev. 2012, 41, 1323−1349. (23) Haase, M.; Schäfer, H. Upconverting Nanoparticles. Angew. Chem., Int. Ed. 2011, 50, 5808−5829. (24) Gai, S.; Li, C.; Yang, P.; Lin, J. Recent Progress in Rare Earth Micro/Nanocrystals: Soft Chemical Synthesis, Luminescent Properties, and Biomedical Applications. Chem. Rev. 2014, 114, 2343−2389. (25) Lusic, H.; Grinstaff, M. W. X-Ray-Computed Tomography Contrast Agents. Chem. Rev. 2013, 113, 1641−1666. (26) Liu, Y.; Ai, K.; Liu, J.; Yuan, Q.; He, Y.; Lu, L. A HighPerformance Ytterbium-Based Nanoparticulate Contrast Agent for in Vivo X-Ray Computed Tomography Imaging. Angew. Chem., Int. Ed. 2012, 51, 1437−1442. (27) Liu, Y.; Ai, K.; Lu, L. Nanoparticulate X-Ray Computed Tomography Contrast Agents: From Design Validation to in Vivo Applications. Acc. Chem. Res. 2012, 45, 1817−1827. (28) Chen, G.; Ohulchanskyy, T. Y.; Liu, S.; Law, W.-C.; Wu, F.; Swihart, M. T.; Ågren, H.; Prasad, P. N. Core/Shell NaGdF4:Nd3+/ NaGdF4 Nanocrystals with Efficient Near-Infrared to Near-Infrared Downconversion Photoluminescence for Bioimaging Applications. ACS Nano 2012, 6, 2969−2977. (29) Wang, R.; Zhou, L.; Wang, W.; Li, X.; Zhang, F. In Vivo Gastrointestinal Drug-Release Monitoring through Second NearInfrared Window Fluorescent Bioimaging with Orally Delivered Microcarriers. Nat. Commun. 2017, 8, 14702. (30) Liu, B.; Li, C.; Yang, P.; Hou, Z.; Lin, J. 808-nm-Light-Excited Lanthanide-Doped Nanoparticles: Rational Design, Luminescence Control and Theranostic Applications. Adv. Mater. 2017, 29, 1605434.

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (W.F.). *E-mail: [email protected] (F.L.). ORCID

Wei Feng: 0000-0002-8096-2212 Fuyou Li: 0000-0001-8729-1979 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS F.L. received funding from the State Key Basic Research Program of China 2015CB931800 and the National Natural Science Foundation of China 21231004, 21375024, and 21527801; F.W. received funding from the State Key Basic Research Program of China 2013CB733700, the National Natural Science Foundation of China 21671042, and the Shanghai Sci. Tech. Comm 15QA1400700.

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REFERENCES

(1) Song, X.; Chen, Q.; Liu, Z. Recent Advances in the Development of Organic Photothermal Nano-Agents. Nano Res. 2014, 8, 340−354. (2) Cheng, L.; Wang, C.; Feng, L.; Yang, K.; Liu, Z. Functional Nanomaterials for Phototherapies of Cancer. Chem. Rev. 2014, 114, 10869−10939. (3) Jaque, D.; Maestro, L. M.; del Rosal, B.; Haro-Gonzalez, P.; Benayas, A.; Plaza, J. L.; Rodríguez, E. M.; Solé, J. G. Nanoparticles for Photothermal Therapies. Nanoscale 2014, 6, 9494−9530. (4) Chen, H.; Shao, L.; Ming, T.; Sun, Z.; Zhao, C.; Yang, B.; Wang, J. Understanding the Photothermal Conversion Efficiency of Gold Nanocrystals. Small 2010, 6, 2272−2280. (5) Huang, X.; Tang, S.; Mu, X.; Dai, Y.; Chen, G.; Zhou, Z.; Ruan, F.; Yang, Z.; Zheng, N. Freestanding Palladium Nanosheets with Plasmonic and Catalytic Properties. Nat. Nanotechnol. 2011, 6, 28−32. (6) Dykman, L. A.; Khlebtsov, N. G. Multifunctional Gold-Based Nanocomposites for Theranostics. Biomaterials 2016, 108, 13−34. (7) Jiang, B.-P.; Hu, L.-F.; Shen, X.-C.; Ji, S.-C.; Shi, Z.; Liu, C.-J.; Zhang, L.; Liang, H. One-Step Preparation of a Water-Soluble Carbon Nanohorn/Phthalocyanine Hybrid for Dual-Modality Photothermal and Photodynamic Therapy. ACS Appl. Mater. Interfaces 2014, 6, 18008−18017. (8) Wang, X.; Wang, C.; Cheng, L.; Lee, S.-T.; Liu, Z. Noble Metal Coated Single-Walled Carbon Nanotubes for Applications in Surface Enhanced Raman Scattering Imaging and Photothermal Therapy. J. Am. Chem. Soc. 2012, 134, 7414−7422. (9) Hessel, C. M.; Pattani, V. P.; Rasch, M.; Panthani, M. G.; Koo, B.; Tunnell, J. W.; Korgel, B. A. Copper Selenide Nanocrystals for Photothermal Therapy. Nano Lett. 2011, 11, 2560−2566. (10) Tian, Q.; Hu, J.; Zhu, Y.; Zou, R.; Chen, Z.; Yang, S.; Li, R.; Su, Q.; Han, Y.; Liu, X. Sub-10 nm Fe3O4@Cu2‑xS Core−Shell Nanoparticles for Dual-Modal Imaging and Photothermal Therapy. J. Am. Chem. Soc. 2013, 135, 8571−8577. (11) Liu, Y.; Ai, K.; Liu, J.; Deng, M.; He, Y.; Lu, L. DopamineMelanin Colloidal Nanospheres: An Efficient Near-Infrared Photothermal Therapeutic Agent for in Vivo Cancer Therapy. Adv. Mater. 2013, 25, 1353−1359. (12) Dong, Z.; Gong, H.; Gao, M.; Zhu, W.; Sun, X.; Feng, L.; Fu, T.; Li, Y.; Liu, Z. Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-Guided Cancer Combination Therapy. Theranostics 2016, 6, 1031−1042. (13) Miao, Z.-H.; Wang, H.; Yang, H.; Li, Z.-L.; Zhen, L.; Xu, C.-Y. Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells. ACS Appl. Mater. Interfaces 2015, 7, 16946−16952. (14) Zhang, D.; Wu, M.; Zeng, Y.; Wu, L.; Wang, Q.; Han, X.; Liu, X.; Liu, J. Chlorin E6 Conjugated Poly(Dopamine) Nanospheres as 26682


Research Article


(51) Smith, A. M.; Mancini, M. C.; Nie, S. Bioimaging: Second Window for in Vivo Imaging. Nat. Nanotechnol. 2009, 4, 710−711. (52) Welsher, K.; Sherlock, S. P.; Dai, H. Deep-Tissue Anatomical Imaging of Mice Using Carbon Nanotube Fluorophores in the Second Near-Infrared Window. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 8943− 8948. (53) Xia, A.; Chen, M.; Gao, Y.; Wu, D.; Feng, W.; Li, F. Gd3+ Complex-Modified NaLuF4-Based Upconversion Nanophosphors for Trimodality Imaging of NIR-to-NIR Upconversion Luminescence, XRay Computed Tomography and Magnetic Resonance. Biomaterials 2012, 33, 5394−5405. (54) Zhou, J.; Zhu, X.; Chen, M.; Sun, Y.; Li, F. Water-Stable NaLuF4-based Upconversion Nanophosphors with Long-Term Validity for Multimodal Lymphatic Imaging. Biomaterials 2012, 33, 6201−6210. (55) Yang, Y.; Liu, J.; Liang, C.; Feng, L.; Fu, T.; Dong, Z.; Chao, Y.; Li, Y.; Lu, G.; Chen, M.; Liu, Z. Nanoscale Metal−Organic Particles with Rapid Clearance for Magnetic Resonance Imaging-Guided Photothermal Therapy. ACS Nano 2016, 10, 2774−2781. (56) Yu, M.; Zheng, J. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles. ACS Nano 2015, 9, 6655−6674.

(31) Feng, Y.; Xiao, Q.; Zhang, Y.; Li, F.; Li, Y.; Li, C.; Wang, Q.; Shi, L.; Lin, H. Neodymium-Doped NaHoF4 Nanoparticles as NearInfrared Luminescent/T2-Weighted MR Dual-Modal Imaging Agents in Vivo. J. Mater. Chem. B 2017, 5, 504−510. (32) Liu, Q.; Sun, Y.; Li, C.; Zhou, J.; Li, C.; Yang, T.; Zhang, X.; Yi, T.; Wu, D.; Li, F. 18F-Labeled Magnetic-Upconversion Nanophosphors Via Rare-Earth Cation-Assisted Ligand Assembly. ACS Nano 2011, 5, 3146−3157. (33) Sun, Y.; Zhu, X.; Peng, J.; Li, F. Core−Shell Lanthanide Upconversion Nanophosphors as Four-Modal Probes for Tumor Angiogenesis Imaging. ACS Nano 2013, 7, 11290−11300. (34) Liu, Y.; Ai, K.; Lu, L. Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields. Chem. Rev. 2014, 114, 5057−5115. (35) Liu, X.; Cao, J.; Li, H.; Li, J.; Jin, Q.; Ren, K.; Ji, J. MusselInspired Polydopamine: A Biocompatible and Ultrastable Coating for Nanoparticles in Vivo. ACS Nano 2013, 7, 9384−9395. (36) Zhong, X.; Yang, K.; Dong, Z.; Yi, X.; Wang, Y.; Ge, C.; Zhao, Y.; Liu, Z. Polydopamine as a Biocompatible Multifunctional Nanocarrier for Combined Radioisotope Therapy and Chemotherapy of Cancer. Adv. Funct. Mater. 2015, 25, 7327−7336. (37) Sun, T.; Li, Z.-J.; Wang, H.-G.; Bao, D.; Meng, F.-L.; Zhang, X.B. A Biodegradable Polydopamine-Derived Electrode Material for High-Capacity and Long-Life Lithium-Ion and Sodium-Ion Batteries. Angew. Chem., Int. Ed. 2016, 55, 10662−10666. (38) Kim, B. H.; Lee, D. H.; Kim, J. Y.; Shin, D. O.; Jeong, H. Y.; Hong, S.; Yun, J. M.; Koo, C. M.; Lee, H.; Kim, S. O. Mussel-Inspired Block Copolymer Lithography for Low Surface Energy Materials of Teflon, Graphene, and Gold. Adv. Mater. 2011, 23, 5618−5622. (39) Kang, S. M.; You, I.; Cho, W. K.; Shon, H. K.; Lee, T. G.; Choi, I. S.; Karp, J. M.; Lee, H. One-Step Modification of Superhydrophobic Surfaces by a Mussel-Inspired Polymer Coating. Angew. Chem., Int. Ed. 2010, 49, 9401−9404. (40) Dreyer, D. R.; Miller, D. J.; Freeman, B. D.; Paul, D. R.; Bielawski, C. W. Elucidating the Structure of Poly(Dopamine). Langmuir 2012, 28, 6428−6435. (41) Ye, Q.; Zhou, F.; Liu, W. Bioinspired Catecholic Chemistry for Surface Modification. Chem. Soc. Rev. 2011, 40, 4244−4258. (42) Lee, H.; Dellatore, S. M.; Miller, W. M.; Messersmith, P. B. Mussel-Inspired Surface Chemistry for Multifunctional Coatings. Science 2007, 318, 426−430. (43) Lynge, M. E.; van der Westen, R.; Postma, A.; Städler, B. Polydopaminea Nature-Inspired Polymer Coating for Biomedical Science. Nanoscale 2011, 3, 4916−4928. (44) Liu, F.; He, X.; Lei, Z.; Liu, L.; Zhang, J.; You, H.; Zhang, H.; Wang, Z. Facile Preparation of Doxorubicin-Loaded Upconversion@ Polydopamine Nanoplatforms for Simultaneous in Vivo Multimodality Imaging and Chemophotothermal Synergistic Therapy. Adv. Healthcare Mater. 2015, 4, 559−568. (45) Liu, T.; Li, S.; Liu, Y.; Guo, Q.; Wang, L.; Liu, D.; Zhou, J. MnComplex Modified NaDyF 4 :Yb@NaLuF 4:Yb,Er@Polydopamine Core−Shell Nanocomposites for Multifunctional Imaging-Guided Photothermal Therapy. J. Mater. Chem. B 2016, 4, 2697−2705. (46) Roper, D. K.; Ahn, W.; Hoepfner, M. Microscale Heat Transfer Transduced by Surface Plasmon Resonant Gold Nanoparticles. J. Phys. Chem. C 2007, 111, 3636−3641. (47) Liu, Q.; Feng, W.; Yang, T.; Yi, T.; Li, F. Upconversion Luminescence Imaging of Cells and Small Animals. Nat. Protoc. 2013, 8, 2033−2044. (48) Wang, J.; Shah, Z. H.; Zhang, S.; Lu, R. Silica-Based Nanocomposites Via Reverse Microemulsions: Classifications, Preparations, and Applications. Nanoscale 2014, 6, 4418−4437. (49) Zarur, A. J.; Ying, J. Y. Reverse Microemulsion Synthesis of Nanostructured Complex Oxides for Catalytic Combustion. Nature 2000, 403, 65−67. (50) Zou, H. Y.; Gao, P. F.; Gao, M. X.; Huang, C. Z. PolydopamineEmbedded Cu2‑xSe Nanoparticles as a Sensitive Biosensing Platform through the Coupling of Nanometal Surface Energy Transfer and Photo-Induced Electron Transfer. Analyst 2015, 140, 4121−4129. 26683


Mussel-Inspired Polydopamine-Coated Lanthanide Nanoparticles for

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