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.

中文翻译：

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基于丝胶蛋白的纳米粒子作为光敏剂氯霉素e6载体，用于增强癌症的光动力治疗

由于具有无创性，治疗灵活性和非全身毒性的优点，光动力疗法（PDT）在对抗恶性癌症方面具有广阔的前景。传统PDT的问题，包括大多数光敏剂（PSs）的严重疏水性，在肿瘤部位的不良聚集以及潜在的长期副作用，极大地削弱了其治疗功效。因此，预期纳米化学系统将有助于我们抗击癌症。本文中，我们合理设计了基于丝绢胶蛋白（SS）的纳米颗粒（称为SSC NPs），其中光敏剂二氢卟酚e6（Ce6）通过简单的酰胺化反应与水溶性SS偶联，以增强成像引导的PDT。与游离的Ce6相比，如此制备的SSC NPs显示出更高的细胞内摄取效率和对肿瘤球的渗透性。^-2），表明它们作为PDT纳米剂具有良好的生物相容性和可行性。在对4T1荷瘤小鼠进行全身给药后，与游离Ce6相比，SSC NPs在肿瘤部位获得了更好的蓄积，这可能有助于延长纳米级药物的血液循环。体内研究表明，与游离Ce6相比，SSC NPs更有效地抑制了肿瘤的生长，并且对被治疗的动物没有明显的副作用。综上所述，这些结果表明，SSC NP作为基于SS的光疗癌症的替代候选者具有令人兴奋的机会。