In Vivo Targeted Deep-Tissue Photodynamic Therapy Based on Near-Infrared Light Triggered Upconversion Nanoconstruct

Abstract

Two major challenges of current photodynamic therapy (PDT) are the limited tissue penetration of excitation light and poor tumor-selectivity of the photosensitizer (PS). To address these issues, we developed a multifunctional nanoconstruct consisting of upconversion nanoparticles (UCNPs) that transform near-infrared (NIR) light to visible light and a photosensitizer zinc(II) phthalocyanine (ZnPc). Folate-modified amphiphilic chitosan (FASOC) was coated on the surface of UCNPs to anchor the ZnPc close to the UCNPs, thereby facilitating resonance energy transfer from UCNPs to ZnPc. Confocal microscopy and NIR small animal imaging demonstrated the enhanced tumor-selectivity of the nanoconstructs to cancer cells that overexpressed folate receptor. Reactive oxygen species (ROS) generation in cancer cells under a 1-cm tissue was higher upon excitation of UCNPs with the 980 nm light than that with 660 nm irradiation. In vivo PDT treatments for deep-seated tumors demonstrated that NIR light-triggered PDT based on the nanoconstructs possessed remarkable therapeutic efficacy with tumor inhibition ratio up to 50% compared with conventional visible light-activated PDT with a noticeable reduced tumor inhibition ratio of 18%. These results indicate that the multifunctional nanoconstruct is a promising PDT agent for deep-seated tumor treatment and demonstrate a new paradigm for enhancing PDT efficacy.

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