Silk Sericin-Based Nanoparticle as the Photosensitizer Chlorin e6 Carrier for Enhanced Cancer Photodynamic Therapy

With the merits of noninvasiveness, flexibility of treatment, and nonsystemic toxicity, photodynamic therapy (PDT) holds great promise in fighting against malignant cancers. Issues with conventional PDT, including severe hydrophobicity of the majority of photosensitizers (PSs), poor accumulation at the tumor site, and potential long-term side effects, greatly attenuate its therapeutic efficacy. Nanotheranostic systems are thus expected to assist our battle against cancer. Herein, we rationally designed the silk sericin (SS) based nanoparticles (designated as SSC NPs), in which photosensitizer chlorin e6 (Ce6) was conjugated with water-soluble SS via simple amidation reaction, for enhanced imaging-guided PDT. Compared with free Ce6, the as-prepared SSC NPs showed enhanced intracellular uptake efficiency and penetrability into tumor spheres. Furthermore, the SSC NPs exhibited negligible cytotoxicity toward 4T1 cells in darkness, while presenting a remarkable anticancer effect under a reduced laser power density (660 nm, 100 mW cm−2), indicating their good biocompatibility and feasibility as PDT nanoagents. Following systemic administration in 4T1 tumor-bearing mice, the SSC NPs achieved superior accumulation in tumor sites in comparison with free Ce6, which might contribute to prolonged blood circulation of nanoscale drugs. In vivo studies revealed that SSC NPs suppress the growth of tumors more effectively compared to free Ce6 and did not induce apparent side effects to the treated animals. Taken together, these results indicate that the SSC NPs have an exciting opportunity as an alternative candidate for SS-based phototherapy of cancer.