NIR-responsive polypeptide copolymer upconversion composite nanoparticles for triggered drug release and enhanced cytotoxicity†
Abstract
Near infrared (NIR) light-responsive polymeric nanomedicines might achieve spatiotemporal, pulsatile, and on-demand drug release profiles and are appealing as a noninvasive technology for various clinical therapies. Polypeptide copolymer composite nanoparticles with different amounts of upconversion nanoparticles (UCNPs) were successfully fabricated in aqueous solution, and the NIR sensitivity of the composite nanoparticles was characterized by time-resolved UV-vis spectroscopy, on-line dynamic light scattering, and transmission electron microscopy. The composite nanoparticles disassembled with the help of UCNPs converting NIR light into UV light, and the NIR-responsive time can be tuned by both the loaded amount of UCNPs and the polypeptide chain length. The composite nanoparticles loaded with the anticancer drug doxorubicin (DOX) can release DOX in a controllable and/or pulsatile manner, and the drug release profile can be manipulated by NIR light. The DOX-loaded composite nanoparticles can be quickly internalized by HeLa cells and then release DOX inside the cells, as evidenced by flow cytometry and confocal laser scanning microscopy. After 5 or 10 min of NIR irradiation, the half maximal inhibitory concentration (IC50) for the DOX-loaded composite nanoparticles dropped to 5.08 μg DOX equiv. mL−1 or 2.95 μg DOX equiv. mL−1, respectively, compared to 8.26 μg DOX equiv. mL−1 for the non-irradiated sample, demonstrating a tunable NIR-triggered cytotoxicity. This work provides a versatile platform for the fabrication of NIR-responsive polypeptide copolymer nanomedicines with the potential for on-demand drug delivery and cancer therapy.