Self-assembly of nanomicelles with rationally designed multifunctional building blocks for synergistic chemo-photodynamic therapy.
Self-assembly of nanomicelles with rationally designed multifunctional building blocks for synergistic chemo-photodynamic therapy.
复制标题
具有合理设计的多功能构建块的纳米胶束的自组装，用于协同化学光动力学治疗。
作者：
Gong G;Pan J;He Y;Shang J;Wang X;Zhang Y;Zhang G;Wang F;Zhao G;Guo J
原理：将光敏剂、供氧剂和辅助治疗药物组合在一个单一的纳米药物递送系统中用于光动力治疗(PDT)，已经显示出克服PDT在肿瘤治疗中固有挑战的巨大希望。然而，集成多个组件的复杂准备阻碍了它们的进一步发展。在这里，我们描述了一种具有合理设计的积木的自组装纳米胶束，它在动物模型中显示了协同化学光动力学治疗的高效率。方法：通过配位驱动自组装，将二茂铁环钯化合物与光敏剂和透明质酸偶联，制备纳米胶束(简称FCP-TPH/HA)。考察了FCP-TPH/HA的形态、靶向给药、药代动力学、溶血和多模式协同治疗。结果：纳米胶束的形成具有低的溶血率和延长的血液循环时间。FCP-TPH/HA通过HA与CD44的特异性结合以及联合化疗和自供氧PDT，在体外具有增强的抗肿瘤作用。同时，在体内乳腺癌模型上，纳米胶束有助于显著提高抗肿瘤效果(肿瘤消退90%)。结论：我们的结果提出了一种模块化的自组装纳米胶束平台，具有协同的化学-光动力学治疗，以挑战基于PDT的肿瘤治疗。
Rationale: The combination of photosensitizers, oxygen supply agents, and adjuvant therapy drugs in a single nano-drug delivery system for photodynamic therapy (PDT) has been showing great promises to overcome the inherent challenges of PDT for tumor treatment. However, the complicated preparation of integrating multiple components hampers their further developments. Here, we describe a self-assembly nanomicelle with rationally designed building blocks, which shows a high efficiency of synergistic chemo-photodynamic therapy in the animal modal. Methods: The nanomicelle was prepared by a coordination-driven self-assembly based on a rationally designed ferrocene cyclopalladated compound coupled with photosensitizers and hyaluronic acid (referred to as FCP-Tph/HA). The morphology, targeting drug delivery, pharmacokinetics, hemolysis, and multimodal synergistic therapy of FCP-Tph/HA were investigated. Results: The formation of nanomicelles presents a low hemolysis rate and a prolonged blood circulation time. FCP-Tph/HA possesses an enhanced antitumor effect in vitro through the specific binding of HA to CD44 and combining chemotherapy with oxygen self-supplying PDT. Simultaneously, the nanomicelle facilitates a significantly improved antitumor efficacy (>90% tumor regression) on a breast cancer model in vivo. Conclusion: Our results present a modular self-assembled nanomicellar platform with synergistic chemo-photodynamic therapy for challenging PDT-based tumor treatment.