A Novel Theranostic Nanoplatform Based on Pd@Pt-PEG-Ce6 for Enhanced Photodynamic Therapy by Modulating Tumor Hypoxia Microenvironment

Photodynamic therapy (PDT), which utilizes reactive oxygen species to kill cancer cells, has found wide applications in cancer treatment. However, the hypoxic nature of most solid tumors can severely restrict the efficiency of PDT. Meanwhile, the hydrophobicity and limited tumor selectivity of some photosensitizers also reduce their PDT efficacy. Herein, a photosensitizer-Pd@Pt nanosystem (Pd@Pt-PEG-Ce6) is designed for highly efficient PDT by overcoming these limitations. In the nanofabrication, Pd@Pt nanoplates, exhibiting catalase-like activity to decompose H2O2 to generate oxygen, are first modified with bifunctional PEG (SH-PEG-NH2). Then the Pd@Pt-PEG is further covalently conjugated with the photosensitizer chlorin e6 (Ce6) to get Pd@Pt-PEG-Ce6 nanocomposite. The Pd@Pt-PEG-Ce6 exhibits good biocompatibility, long blood circulation half-life, efficient tumor accumulation, and outstanding imaging properties. Both in vitro and in vivo experimental results clearly indicate that Pd@Pt-PEG-Ce6 effectively delivers photosensitizers to cancer cells/tumor sites and triggers the decomposition of endogenous H2O2 to produce oxygen, resulting in a remarkably enhanced PDT efficacy. Moreover, the moderate photothermal effect of Pd@Pt nanoplates also strengthen the PDT of Pd@Pt-PEG-Ce6. Therefore, by integrating the merits of high tumor-specific accumulation, hypoxia modulation function, and mild photothermal effect into a single nanoagent, Pd@Pt-PEG-Ce6 readily acts as an ideal nanotherapeutic platform for enhanced cancer PDT.