Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, PR China; School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus, Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, PR China.
School of Physics and Physical Engineering, Qufu Normal University, Qufu 273165, PR China; Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
Pharmacol Res. 2024 May;203:107150. doi: 10.1016/j.phrs.2024.107150. Epub 2024 Mar 21.
Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as a viable alternative to conventional cancer treatments that encounter drug resistance. Nanotechnology has brought new advances in medicine and has shown great potential in drug delivery and cancer treatment. For precise and efficient therapeutic utilization of such a tumor therapeutic approach with high spatiotemporal selectivity and minimal invasiveness, the carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination therapy is essential. Utilizing natural products as the foundation for nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, and well biocompatibility. The natural-product-based, carrier-free, noncovalent NPs revealed excellent synergistic anticancer activity in comparison with free photosensitizers and free bioactive natural products, representing an alternative and favorable combination therapeutic avenue to improve therapeutic efficacy. Herein, a comprehensive summary of current strategies and representative application examples of carrier-free noncovalent NPs in the past decade based on natural products (such as paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, and curcumin) for tumor chemo-photodynamic combination therapy. We highlight the insightful design and synthesis of the smart carrier-free NPs that aim to enhance PDT efficacy. Meanwhile, we discuss the future challenges and potential opportunities associated with these NPs to provide new enlightenment, spur innovative ideas, and facilitate PDT-mediated clinical transformation.
癌症的多样性、异质性和复杂性使其成为全球发病率、残疾率和死亡率的主要原因，这凸显了变革性治疗方法的必要性。光动力疗法 (PDT) 作为一种替代传统癌症治疗方法的可行方案，因其能够克服耐药性而引起了持续关注。纳米技术在医学领域带来了新的进展，在药物输送和癌症治疗方面显示出巨大的潜力。为了实现这种具有高时空选择性和最小侵入性的肿瘤治疗方法的精确和高效治疗利用，基于化学-光动力联合治疗的无载体非共价纳米颗粒 (NPs) 是必不可少的。利用天然产物作为纳米药物开发的基础具有无与伦比的优势，包括卓越的药理学活性、易于功能化/修饰和良好的生物相容性。与游离光敏剂和游离生物活性天然产物相比，基于天然产物的无载体非共价 NPs 表现出优异的协同抗癌活性，为提高治疗效果提供了一种替代和有利的联合治疗途径。本文全面总结了过去十年中基于天然产物（如紫杉醇、10-羟基喜树碱、阿霉素、依托泊苷、康普瑞汀 A4、表没食子儿茶素没食子酸酯和姜黄素）的无载体非共价 NPs 在肿瘤化学-光动力联合治疗中的最新策略和代表性应用实例。我们强调了旨在增强 PDT 疗效的智能无载体 NPs 的巧妙设计和合成。同时，我们讨论了这些 NPs 面临的未来挑战和潜在机遇，为 PDT 介导的临床转化提供新的启示、激发创新思路。
