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Abstract
Rapid drug release at the specific site of action is still a challenge for antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides a promising strategy to enhance therapeutic effects by combining the unique features of each component. The present study explored the use of drug–gold nanoparticle conjugates incorporated into liposomes to enhance antitumor efficiency. A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier transform infrared spectroscopy, and differential scanning calorimetry. The conjugates were incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm) with light-responsive release properties, as shown by in vitro release studies. Intracellular uptake and distribution was studied in HeLa cells using transmission electron microscopy and confocal laser scanning microscopy. This demonstrated liposome internalization and localization in endosomal–lysosomal vesicles. Fluorescence intensity increased in cells exposed to UV light, indicating that this stimulated intracellular drug release; this finding was confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared liposomes coupled with UV light exposure produced greater antitumor effects in nude mice and reduced side effects, as compared with free vincristine sulfate.
Supplementary materials
Figure S1 (A) FTIR spectra of (a) gold nanoparticles; (b) VCR; and (c) VGC. (B) DSC curves of (a) gold nanoparticles; (b) VCR; and (c) VGC. (C) DSC curves of (a) BL; (b) VGC; (c) VGC-L.
Abbreviations: FTIR, fourier transform infrared spectroscopy; VCR, vincristine sulfate; VGC, vincristine sulfate-gold nanoparticles conjugates; DSC, differential scanning calorimetry; BL, blank liposomes; VGC-L, vincristine sulfate-gold nanoparticles conjugates loaded liposomes.
Figure S2 Microscope images of control HeLa cells and those incubated with VCR-L, VGC-L, and VGC-L plus UV light.
Abbreviations: VCR-L, vincristine sulfate-loaded liposomes; VGC-L, vincristine sulfate-gold nanoparticles conjugates loaded liposomes.
Acknowledgments
This work was supported financially by the National Science Foundation of China (No 81195925, No 81283232) and Shanghai Natural Science Foundation Project (11ZR1416193).
Disclosure
The authors report no conflicts of interest in this work.