Near-Infrared Light-Initiated Upconversion Nanoplatform with Tumor Microenvironment Responsiveness for Improved Photodynamic Therapy.

Abstract

Photodynamic therapy (PDT) is inflowing the mainstream of the cancer treatments, yet the shallow light penetration, thermal damage to normal cells, poor tumor targeting, and skin phototoxicity compromised the PDT efficacy. This paper designed and prepared an upconversion nanoplatform that could effectively convert 808 nm NIR light to red and green light emission, both of which could excite photosensitizers and exert the PDT curative effects. A thin layer of mesoporous silica covering core-shell nanostructure NaGdF4:Yb,Er@NaGdF4:Yb,Nd upconversion nanoparticles was prepared as the carrier to load the photosensitizer pyropheophorbide-a (PPa), which could be excited by green and red light simultaneously and produce high singlet oxygen (1O2) quantum yield (79.1%). Meanwhile, the chemotherapy drug doxorubicin (DOX) was absorbed in the pores of the SiO2 layer to improve the therapeutic effect, and the folic acid-coupled chitosan (Cs-FA) was modified on the surface of the SiO2 layer to obtain the targeting and biocompatible UCNP@SiO2/PPa&DOX@Cs-FA nanoplatform. The physically adsorbed DOX in the pore channel could be released slowly under faintly acidic or GSH stimuli (84% release of DOX after 16 h), suggesting that the nanoplatform was responsive to the tumor microenvironment. In vitro experiments showed that the combined treatment of PDT and DOX was superior to that of PDT alone or DOX chemotherapy alone, implying a synergistic therapeutic effect. The morphological changes and dye staining research of HeLa cells were consistent with the MTT assay. Therefore, this research provided a strategy for the development of an efficient and safe multifunctional cancer treatment nanoplatform integrating low-intensity light excitation, slow release, targeting, photodynamic therapy, and chemotherapy.