光动力疗法与化学药物输送系统的整合在增强抗癌治疗方面显示出巨大的潜力。然而，化疗剂和光敏剂的溶解度和非特异性生物分布继续构成阻碍其临床应用的挑战。基于多肽的纳米级药物递送系统的制备来解决上述问题。通过将光敏剂二氢卟酚e6（Ce6）缀合到多肽聚（L-赖氨酸）-b-聚苯丙氨酸（PKF）上形成两亲性聚合物，用于封装模型药物二聚喜树碱（DCPT），以及具有高活性的纳米颗粒（PCD）。用酸敏感的聚乙二醇（PEG）进一步修饰载药效率，得到药物递送系统（PPCD）。DCPT和Ce6的包封率分别为99%和73.5%。在pH为7.4的磷酸盐缓冲盐水（PBS）溶液中，PEG外壳提高了胶束的稳定性并屏蔽了其正电荷，而在酸性肿瘤微环境中，pH敏感的PEG层被去除以暴露出阳离子纳米粒子，从而促进 PPCD 胶束的细胞摄取。受益于增强的细胞内化，经过PCD和PPCD胶束处理的细胞内活性氧（ROS）的量明显增加。此外，通过细胞和动物研究验证了PPCD胶束增强的抗癌功效。这项研究提出了一种有前途的方法来促进化疗剂和光敏剂的溶解度和生物分布，从而促进化学光动力癌症治疗的进一步应用.© 2023. 国际中医药学会和生物医学中心有限公司

The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.A polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.© 2023. International Society for Chinese Medicine and BioMed Central Ltd.