Article pubs.acs.org/Macromolecules
Nanocomposites of Spiropyran-Functionalized Polymers and Upconversion Nanoparticles for Controlled Release Stimulated by Near-Infrared Light and pH Shuo Chen,†,§ Yujuan Gao,‡ Ziquan Cao,† Bo Wu,† Lei Wang,*,‡ Hao Wang,*,‡ Zhimin Dang,*,§ and Guojie Wang*,† †
School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China Laboratory of Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology (NCNST), Chinese Academy of Sciences, Beijing 100864, China § Department of Polymer Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China ‡
S Supporting Information *
ABSTRACT: Here a near-infrared light and pH responsive nanocomposite comprising spiropyran-functionalized amphiphilic polymers and upconversion nanoparticles (UCNPs) is reported, which is prepared through the selfassembly of the amphiphilic polymers and the encapsulation of the UCNPs in the core of the self-assemblies. Upon near-infrared light irradiation, the upconversion fluorescence can induce the hydrophobic spiropyran to be isomerized to the hydrophilic merocyanine and disrupt the spherical morphology of the nanocomposites. Meanwhile, at low pH, the hydrophobic spiropyran can be also protonated to become hydrophilic merocyanine, and the self-assemblies are swollen. Model molecules, hydrophobic Coumarin 102, are demonstrated to be released from the nanocomposites triggered by the near-infrared light and acidic pH. In addition, the cytotoxicity of the nanocomposites loaded with anticancer drugs Doxorubicin on cancer cells indicates that the loaded drugs can be released and kill the cells effectively and the efficiency can be enhanced significantly upon near-infrared light irradiation.
1. INTRODUCTION Controlled drug-release devices have emerged widely for drug delivery which adapt for various internal or external stimuli, such as light, pH, redox, and temperature.1−7 Different from other stimuli, light is a clean and highly efficient source which can be triggered outside of the system and controlled spatially and temporally with great ease and convenience.8−10 Most of the phototriggered drug-release devices are depended on ultraviolet (UV) light and visible light stimulation, while the low penetration depth of the lights and the harmfulness to living tissues of UV light will limit their practical applications. Compared to UV and visible light, near-infrared (NIR) light is more suitable for biomedical applications since NIR light is able to penetrate into deeper tissues without photodamage.11−13 Lanthanide-doped upconversion nanoparticles can absorb NIR photons and convert low-energy photons into high-energy photons based on the anti-Stokes process,14,15 which have been applied in the fields of drug delivery16−24 and biological labeling and imaging.25−28 Multifunctional nanocarriers based on the UCNPs core and thermo/pH-coupling sensitive polymer gated mesoporous silica shell have been reported for cancer theranostics, including fluorescence imaging, and for controlled drug release for therapy.29 Mesoporous silica coated upcoverting nanoparticles loaded with anticancer drug Doxorubicin and © XXXX American Chemical Society
grafted with ruthenium complexes as photoactive molecular valves have also been prepared for drug delivery.30 Using a nitrobenzene-based photosensitive hybrid hydrogel loaded with UCNPs, Zhao et al. showed that NIR light could be used to induce the gel−sol transition and release large, inactive biomacromolecules (protein and enzyme) entrapped in the hydrogels into aqueous solution.31 Herein, we report a near-infrared light-responsive nanocomposite comprising spiropyran-functionalized amphiphilic polymers32−34 and upconversion nanoparticles (UCNPs), which can be also responsive to pH. Model molecules, hydrophobic fluorescent dyes Coumarin 102, are demonstrated to be released from the nanocomposites triggered by the nearinfrared light and acidic pH. In addition, the cytotoxicity of the nanocomposites loaded with anticancer drugs Doxorubicin (Dox) on U-87 MG cancer cells indicates that the loaded drugs can kill the cells effectively and the efficiency can be enhanced significantly upon near-infrared light irradiation. Such achievements present that the nanocomposites of spiropyran-functionalized amphiphilic polymers and upconversion nanoparticles Received: August 13, 2016 Revised: September 7, 2016
A
DOI: 10.1021/acs.macromol.6b01760 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules may be applied widely in the field of drug delivery with the advantages of not only the pH responsiveness but also the nearinfrared light responsiveness for its unique characteristics such as no photodamage to the living systems and high tissue penetration depth.35,36
nanocomposites and Dox-loaded UCNPs@Polymer nanocomposites. Briefly, U-87 MG cells were seeded in a 96-well plate (2 × 104 cells per well) and incubated in Dulbecco minimum essential medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% penicillin−streptomycin in a humidified atmosphere of 5% CO2 (37 °C) for 24 h to ensure that the cells had attached to the wells. After that, different materials, such as free DOX·HCl, UCNPs@Polymer nanocomposites, and Dox-loaded UCNPs@Polymer nanocomposites, with different concentrations, were added to each well of the 96-well plate, followed by further incubation for another 2 h. The concentrations of Dox were 0.1, 1, 5, and 10 μg mL−1, respectively. After 2 h incubation in dark, the U-87 MG cells were exposed to a 980 nm laser with power of 4.3 W cm−2 for 7 min. Then, cancer cells were incubated for further 24 h in fresh culture medium. After that, 10 mL of CCK-8 solutions was added to each well and cultured for another 4 h. The absorbance of each sample well and control sample was measured using a Microplate reader at test wavelength of 450 nm and a reference wavelength of 690 nm, respectively. In Vitro Imaging of Dox-Loaded UCNPs@Polymer Nanocomposites. CLSM was employed to observe endocytosis and the release process of DOX. A density of 5 × 105 U-87 MG cells was seeded in the 15 cm culture dishes in DMEM containing 10% FBS and 1% penicillin−streptomycin in a humidified atmosphere with 5% CO2. The cells were first cultured with Dox-loaded nanocomposites for 2 h and then washed with PBS three times. The concentration of Dox was 10 μg mL−1. Then the U-87 MG cells were exposed to a 980 nm laser with power of 4.3 W cm−2 for 7 min. After that, the cells were incubated for further 15 min and 2 h. The cells were incubated with Hoechst (10 mM) for 30 min, and then the cells were washed with PBS to remove the excess fluorescent dye. The cells were imaged using a Zeiss LSM710 CLSM with a 60× objective lens. For quantitative analysis, the background intensity was subtracted from images before analysis. Characterization. The morphologies of the UCNPs@Polymer nanocomposites were characterized with a JEM-2010 EX/S transmission electron microscope (TEM). Dynamic light scattering (DLS) experiments were carried out on the ALV/SP-150 spectrometer equipped with an ALV-5000 multidigital time correlator and a solidstate laser (ADLS DPY 425II, output power ca. 400 MW at λ = 632.8 nm) as the light source. Powder X-ray diffraction was recorded on PANalytical XRD diffractometer using Cu Kα radiation. UV−vis absorption spectra were recorded with a PerkinElmer UV−vis spectrophotometer. The visible light irradiation for the samples was carried out with a high-pressure mercury lamp (520 nm, 20 mW cm−2). Photoirradiation experiments were carried out using a CW IR 980 nm laser (4.3 W cm−2, Thorlabs, Inc.). Fluorescence emission spectra were measured on a HitachiF-4500 fluorescence spectrophotometer equipped with Xeon lamp, in conjugation with a 980 nm diode laser.The U-87 MG cells were imaged using a laser-scanning confocal microscope (Zeiss LSM710) with 60× object lens.
2. EXPERIMENTAL METHODS Materials. The lanthanide chlorides (99.99%) were purchased from Beijing HWRK Chem Co., LTD, and used as starting materials without further purification. Oleic acid (OA, 90% technical grade) and 1-octadecene (ODE, 90% technical grade) were supplied by Alfa Aesar. NaOH (99%), NH4F (99%), methanol (99.5%), cyclohexane (99.5%), and ethanol (99.5%) were all obtained from Beijing Chemical Works. Triethylamine (Et3N, 99.5%), dimethyl sulfoxide (DMSO, 99.9%), and Doxorubicin hydrochloricle (DOX·HCl) were purchased from Sinopharm Chemical Reagent Co. Ltd. Dulbecco minimum essential medium (DMEM) medium, fetal bovine serum (FBS), and phosphate buffered saline (PBS) were obtained from HyClone/ Thermo fisher (Beijing, China). The U-87 MG cell line was purchased from cell culture center of Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (Beijing, China). The spiropyranfunctionalized PNIPAM was synthesized according to a procedure previously published.37 Synthesis of NaYF4:25% Yb, 0.5% Tm Nanocrystals. The UCNPs were prepared according to the previously reported method.38,39 In a typical experiment, 2 mL of LnCl3 (0.745 mmol of YCl3, 0.25 mmol of YbCl3, and 0.005 mmol of TmCl3) in water was added to a 250 mL three-necked round-bottom flask containing 6 mL of OA and 15 mL of ODE. The solution was vigorously stirred at room temperature for 1 h. Then the mixture was slowly heated to 150 °C under N2 flow and maintained for 30 min to form a clear light yellow solution. After cooling down to room temperature, 8 mL of methanol solution of NH4F (0.1482 g, 4 mmol) and NaOH (0.1 g, 2.5 mmol) was slowly added into the flask and vigorously stirred for 2 h at room temperature. Subsequently, the slurry was slowly heated and degassed at 115 °C for 30 min in vacuo to remove methanol and then heated to 300 °C at a constant heating rate of 3.3 °C min−1 under N2 and kept at this temperature for 1 h before it was allowed to cool naturally to room temperature. The mixture were first precipitated by the addition of 10 mL of ethanol and collected by centrifugation at 7500 rpm for 15 min. The product was redispersed with 2 mL of cyclohexane and precipitated by adding 18 mL of ethanol and then collected by the same centrifugation. Preparation of UCNPs@Polymer Nanocomposites and the Nanocomposites Loaded with Coumarin 102. The copolymer (2 mg) and UCNPs (2 mg) were dissolved in THF (1 mL), and then deionized water (1 mL) was added at a rate of 1 μL s−1 with quick stirring to induce the formation of the UCNPs@Polymer nanocomposites. Then 9 mL of deionized water was added to the above solution to quench the formation of the UCNPs@Polymer nanocomposites. THF was removed by dialysis at room temperature for 12 h. As to the UCNPs@Polymer nanocomposites loaded with Coumain 102, the random copolymer (2 mg), UCNPs (2 mg) and Coumain 102 (0.2 mg) were dissolved in THF (1 mL), and then deionized water (1 mL) was added at a rate of 1 μL s−1 with stirring. Then 9 mL of deionized water was added to quench the nanocomposites assembles. THF was removed by dialysis at room temperature for 12 h. Drug Loading. The prodrug DOX·HCl (20 mg) was dissolved in DMSO (2 mL) stirred for 2 h. 15 μL of Et3N was added at rate of 1 μL s−1 to afford free Dox solution. 20 mg mL−1 Dox (0.1 mL), UCNP (2 mg), and SP-based copolymer (2 mg) were dissolved in THF (1 mL). After stirring 2 h, deionized water (1 mL) was added at a rate of 1 μL s−1 to the solution. Then 9 mL of deionized water was added to the above solution to quench the formation of the nanoparticles. THF and DMSO were removed by dialysis at room temperature for 12 h. In Vitro Cell Viability Assay. A typical cell counting kit-8 assay (CCK-8, Beyotime Institute of Biothechnology, China) was carried out to investigate the in vitro cytotoxicity of UCNPs@Polymer
3. RESULTS AND DISCUSSION Scheme 1 represents the fabrication process of the nanocomposites and NIR light and pH controlled release of the loaded guest molecules Coumarin 102. The amphiphilic spiropyran-functionalized copolymers, poly(isopropylacrylamide-co-spiropyran methacrylate)s, can self-assemble into micellar nanoparticles, in which the hydrophobic segments containing spiropyran chromophores form the core and the hydrophilic segments containing poly(isopropylacrylamides) form the shell. Accompanied by the self-assembly of the polymers, the hydrophobic UCNPs and guest molecules such as Coumarin 102 can be encapsulated into the core of the selfassemblies. Upon near-infrared light irradiation, UCNPs emit UV light which induces the isomerization from the hydrophobic spiropyran (SP) to hydrophilic merocyanine (MC).40−45 The isomerization of SP units can disrupt the primary hydrophilic−hydrophobic balance of the self-assemB
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copolymer were determined to be 2.05 × 104 g mol−1 and 1.07, respectively, by gel permeation chromatography (GPC). The molar ratio between NIPAM and SP was determined to be 18:1 tested by a UV−vis absorption spectrometer. We succeeded in loading the UCNPs into the core of micellar nanoparticles by dissolving the polymer and UCNPs in THF and then adding this solution dropwise to water to induce the formation of micellar nanoparticles and the concomitant encapsulation of the UCNPs. Figures 1a and 1b show the TEM images and DLS curves of the UCNPs and UCNPs@Polymer nanocomposites, respectively. The diameter of the prepared UCNPs was about 20−30 nm (Figure 1a). The UCNP was encapsulated in the core of the micellar nanoparticle, and the diameter of the UCNPs@Polymer nanocomposite was about 110−120 nm (Figure 1b). The large-scale TEM image of the polymer-coated UCNPs is shown in Figure S2a. Meanwhile, the UV−vis absorption spectra and upconversion luminescent spectra were employed to demonstrate that UCNPs were encapsulated in the polymer self-assemblies. Figure 1c shows the UV−vis spectra of UCNPs (line 1) and UCNPs@Polymer (line 2). The absorption bands centered at 360 and 980 nm were attributed to SP groups and UCNPs, respectively. Figure 1d shows the emission spectra of the UCNPs (line 1) and the UCNPs@ Polymer (line 2) nanocomposites excited by NIR light (980 nm), from which it can be seen that the emission band centered at 360 nm of the nanocomposites decreased significantly compared with that of the primary UCNPs, indicating that the UV photons delivered by the UCNPs could be absorbed by SP moieties in the nanocomposites. UV−Vis Spectra of the Nanocomposites Stimulated by Near-Infrared and pH. It is known that the upconverted UV light from the UCNPs could be utilized for the photocleavage of nitrobenzyl linkers.52 The emission band centered at 360 nm of the prepared UCNPs overlaps well with the absorption of the SP groups; thus, the isomerization of SP units can be controlled by NIR light irradiation. The UV−vis absorbance change of the SP-functionalized nanocomposites
Scheme 1. Schematic Illustration for Fabrication of the Nanocomposites and NIR Light and pH Controlled Release of the Loaded Coumarin 102
blies, and the nanocomposites will be dissociated, resulting in the release of guest molecules.46−48 At acidic conditions, the hydrophobic SP can be protonated to hydrophilic MC;41 thus, the self-assemblies will be swollen, and the encapsulated Coumarin 102 will be also released. Preparation of UCNPs and Nanocomposites UCNPs@ Polymer. UCNPs NaYF4:25% Yb, 0.5% Tm were synthesized by a seeded growth approach, and the surface of the UCNPs was stabilized with hydrophobic oleic acid ligands.49−51 The composition and phase purity of the UCNPs were confirmed by the XRD data, shown in Figure S1. The amphiphilic copolymer, poly[(N-isopropylacrylamide)-co-(1′-(2-methacryloxyethyl)-3′,3′-dimethyl-6-nitro-spiro(2H-1-benzopyran-2,2′indoline)], was synthesized through copolymerization of hydrophilic N-isopropylacrylamide and light/pH-responsive spiropyran-containing acrylate.37 The number-average molecular weight (Mn) and polydispersity index (PDI) of the
Figure 1. Transmission electron microscope micrographs of the synthesized UCNPs (a) and the nanocomposites UCNPs@Polymer (b). Insets are corresponding size distribution of the synthesized UCNPs and UCNPs@Polymer. (c) UV−vis spectra of UCNPs (1) and UCNPs@Polymer (2). (d) Upconversion luminescence spectra of the synthesized UCNPs (1) and the nanocomposites UCNPs@Polymer (2), excited at 980 nm. C
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Figure 2. UV−vis spectra of the nanocomposites in aqueous solution: (a) irradiated with NIR light (980 nm); (b) then irradiated with visible light (520 nm). (c) UV−vis absorption of the nanocomposites in aqueous solution at 525 nm upon alternate NIR (980 nm) and visible (520 nm) irradiation cycles. (d) UV−vis spectra of the nanocomposites in aqueous solution under pH stimulation.
Figure 3. Release profiles of Coumarin 102 loaded in the UCNPs@Polymer nanocomposites at different conditions: (a) under NIR irradiation for 30 min at different pH values; (b) under different pH values in the absence of NIR irradiation.
isomerize to hydrophilic MC, the polymer self-assemblies were swelled to larger ones with diameter of 245−265 nm, and the hydrophobic UCNPs would be released from the nanocomposites (Figure S2c). When NIR light irradiation was combined with acidic stimulation, the hydrophilicity could be increased further, and the initial spherical nanocomposites were disrupted (Figure S2d). Controlled Release of Model Molecules Coumarin 102 from the Nanocomposites Stimulated by Near-Infrared and pH. The NIR light/pH dual responsive UCNPs@Polymer nanocomposites could be used as smart nanocarriers for controlled release owing to their hydrophobic−hydrophilic switch and morphological changes upon the stimulation. Coumarin 102 was used as a model molecule, and the fluorescence emission spectra of the dye-loaded UCNPs@ Polymer nanocomposites under different stimulation (Figure S5) were investigated to explore the release profile. Figure 3a shows the release profiles of Coumarin 102 under different stimulations. At pH 7 or 5, little of Coumarin 102 could be released from the nanocomposites in the absence of the NIR light in 30 min. At pH 7 with NIR light irradiation, 26% of Coumarin 102 could be released in 30 min, while 34% of the loaded molecules could be released at pH 5 with NIR light irradiation. The control experiment under NIR light irradiation
under NIR light and then visible light irradiation is shown in Figures 2a and 2b. Upon NIR light irradiation, the absorption band centered at 525 nm increased, indicating that SP isomerized to MC (Figure 2a). Then upon visible light irradiation, the absorption band centered at 525 nm reverted to the initial absorption profile, which demonstrated the reverse isomerization of MC → SP (Figure 2b). The reversible nature for the SP units of the UCNPs@Polymer nanocomposites upon exposure to alternating cycles of NIR/vis light irradiation was also investigated. As shown in Figure 2c, the optical switching of the UV−vis absorption was repeated three times, and the reversible switching between SP and MC could be realized upon alternating NIR/vis light irradiation. Figure 2d shows the UV−vis spectra of UCNPs@Polymer nanocomposites under pH stimulation. When adjusting the nanocomposites solution to acidic, a new absorption band centered at 525 nm corresponding to the hydrophilic MC units occurred and increased with the stimulation time, indicating more hydrophilic MC units could be formed. The morphological changes of the UCNPs@Polymer nanocomposites under different stimulations are shown in Figure S2. Upon NIR light irradiation, the UCNPs@Polymer nanocomposites could be dissociated since the photoisomerization of SP → MC (Figure S2b). At acidic conditions, the hydrophobic SP could D
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Figure 4. (a) In vitro cytotoxicity of NIR light, UCNPs@Polymer, and UCNPs@Polymer + NIR light against U-87 MG cells. (b) Cell viability of U87 MG cells incubated individually with Dox-loaded UCNPs@Polymer, DOX·HCl and Dox-loaded UCNPs@Polymer + NIR light. The series of dosage (0.1, 1, 5, and 10 μg mL−1) based on Dox concentration.
indicating that NIR light irradiation and the nanocomposites had little effect on the cell viability, confirmed that the cytotoxicity to cancer cells was caused by release of Dox. The confocal laser scanning microscope (CLSM) observations of the Dox release in U-87 MG cells treated with Doxloaded UCNPs@Polymer nanocomposites are shown in Figure 5. The CLSM images of U-87 MG cells incubated with Dox-
is shown in Figure S6, from which it can be seen that the release of loaded molecules from the polymer nanoparticles without UCNPs is very little although the NIR irradiation could increase the temperature of the system to about 50 °C. Although the release at pH 5 without NIR stimulation in 30 min was negative, the release could be increased with the increase of the pH stimulation time, since more hydrophilic MC units could be formed (Figure 2d). Figure 3b shows the release profile of Coumarin 102 from the nanocomposites under pH stimulation for 24 h. At pH 7, 10% of Coumarin 102 could be released in 24 h, while 69% of the loaded molecules could be released at pH 5. The controlled release of the model molecules Courmarin 102 from the nanocomposites upon NIR/pH stimulation can endow the system with great potential for drug delivery. Application for Drug Delivery in Vitro. Since the cytotoxicity of drug delivery nanocarriers is an important prerequisite and crucial factor for further bioapplications, in vitro cytotoxicity assays of the prepared UCNPs@Polymer nanocomposites and NIR stimulation were carried out by a standard counting kit (CCK-8) assay on U-87 MG cancer cell. Figure 4a shows that the NIR light irradiation, UCNPs@ Polymer nanocomposites, and UCNPs@Polymer nanocomposites upon NIR light irradiation had little effect on the cell viability. This result indicates that UCNPs@Polymer nanocomposites and NIR light have good biocompatibility to satisfy the requirements as potential drug carries for biological applications. Figure 4b shows the cell viability when the cancer cells were incubated with DOX·HCl, Dox-loaded UCNPs@ Polymer nanocomposites, or Dox-loaded UCNPs@Polymer nanocomposites upon NIR light irradiation under different concentrations of Dox in culture media. For the cancer cells in the presence of DOX·HCl, significant cell death was observed when the concentration of Dox increased to 1 μg mL−1. For the cancer cells in the presence of Dox-loaded nanocomposites without NIR light irradiation, there was no significant cell death observed after 24 h of incubation when the concentration of Dox was below 1 μg mL−1. When the concentration increased to 5 μg mL−1, more drugs could be released from the nanocomposites in the intracellular acidic environment (about pH 5),53−55 which killed 60% of the cancer cells. However, for the cancer cells in the presence of Dox-loaded nanocomposites under NIR light irradiation, significant cell death was observed when the concentration of Dox was as low as 0.1 μg mL−1. The control experiments under identical conditions using NIR light or UCNPs@Polymer nanocomposites shown in Figure 4a,
Figure 5. Confocal laser scanning microscope observations of the Dox release in U-87 MG cells treated with Dox-loaded UCNPs@Polymer nanocomposites without NIR light irradiation (a), with NIR light irradiation (7 min, 4.3 W cm−2) and then incubated for 15 min (b), and with the NIR light irradiation and then incubated for 2 h (c). For each panel, the images from left to right show cell nuclei stained by Hoechst (blue; Hoechst 33342), Dox fluorescence in cells (red) and overlays of the two images.
loaded nanocomposites for 15 min are shown in Figure 5a, where intracellular red fluorescence was observed, located in the cytoplasm, demonstrating that Dox was released from the nanocomposites due to the intracellular acidic environment.56 Figure 5b shows the images of the sample with NIR light irradiation (7 min, 4.3 W cm−2) and then incubation for 15 min, from which it can be seen that stronger Dox fluorescence could be observed. The stronger fluorescence indicated the increase of the amount of released Dox upon NIR light irradiation. Figure 5c shows the images of the sample with NIR light irradiation (7 min, 4.3 W cm−2) and then incubation for 2 h, from which it can be seen that the red fluorescence of Dox increased further, indicating that the amount of released Dox E
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could be significantly increased when the incubation duration was extended to a longer time after NIR light irradiation. In contrast, the Dox fluorescence for the samples without NIR irradiation and incubated for 2 h was much lower than that after NIR light irradiation (Figure S6). The significant effect of the NIR light irradiation on killing cells, where more anticancer drugs could be released under combined stimulation of NIR light and intracellular acidic pH, may endow the nanocomposites great potential as promising drug carriers for cancer therapy.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b01760. XRD, TEM images, UV−vis absorption spectra, fluorescence spectra, and CLSM images (PDF)
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REFERENCES
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4. CONCLUSION We have successfully demonstrated the fabrication of UCNPs@ Polymer nanocomposites prepared through the self-assembly of the amphiphilic photoresponsive polymers and the encapsulation of the UCNPs in the core of the self-assemblies. Upon near-infrared light irradiation, the upconversion fluorescence can induce the hydrophobic spiropyran to be isomerized to the hydrophilic merocyanine and disrupt the spherical morphology of the nanocomposites. Meanwhile, at low pH, the hydrophobic spiropyran can be also protonated to hydrophilic merocyanine and the polymer self-assemblies are swollen. Model molecules, hydrophobic fluorescent dyes Coumarin 102, are demonstrated to be released from the nanocomposites triggered by the nearinfrared light and pH 5.0. In addition, the cytotoxicity of the nanocomposites loaded with anticancer drugs Doxorubicin on U-87 MG cancer cells indicates that the loaded drugs can kill the cells effectively and the efficiency can be enhanced significantly upon near-infrared light irradiation. The nanocomposites composed of amphiphilic photoresponsive polymers and upconversion nanoparticles may be applied widely in the field of drug delivery with the advantages of not only the pH responsiveness but also the near-infrared light responsiveness for its unique characteristics such as spatial−temporal control, no photodamage to the living systems, and high tissue penetration depth.
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AUTHOR INFORMATION
Corresponding Authors
*(L.W.) Tel +86-10-62652116; e-mail
[email protected]. *(H.W.) Tel +86-10-62652116; e-mail
[email protected]. *(Z.D.) Tel +86-10-62332599; e-mail
[email protected]. * (G.W.) Tel +86-10-62333619; e-mail guojie.wang@mater. ustb.edu.cn. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We gratefully acknowledge financial support from the National Natural Science Foundation of China (Grants 51373025, 21074010, and 51425201) and the Program for New Century Excellent Talents in University (NCET-11-0582). F
DOI: 10.1021/acs.macromol.6b01760 Macromolecules XXXX, XXX, XXX−XXX
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DOI: 10.1021/acs.macromol.6b01760 Macromolecules XXXX, XXX, XXX−XXX
