Linear Chimeric Triblock Molecules Self-Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo-Photodynamic Therapy of Breast Cancer
Linear Chimeric Triblock Molecules Self-Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo-Photodynamic Therapy of Breast Cancer
复制标题
具有可控变形特性的线性嵌合三嵌段分子自组装胶束可增强乳腺癌化疗光动力疗法的肿瘤保留
DOI：
10.1002/adfm.201808462
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发表时间：
2019-06-01
影响因子：
19
通讯作者：
Gao, Huile
中科院分区：
文献类型：
--
作者：
Liu, Rui;Yu, Meinan;Gao, Huile
尽管纳米颗粒有望彻底改变癌症治疗，但其低疗效仍然是最大的限制因素。近年来的研究发现，纳米粒的黄金原则，增强的渗透性和保留（EPR）的效果，是有限的复杂的肿瘤微环境。在此，新型可转化纳米材料被设计为更有效地利用EPR效应。通过疏水性头部（二氢卟酚e6（Ce 6）或胆红素（BR））、形成氢键的肽（Phe-Phe-Val-Leu-Lys（FFVLK））和亲水性尾部（聚乙二醇（PEG））的串联缀合，合成了在水溶液中可形成胶束的嵌合分子（Ce 6/BR-FFVLK-PEG）。值得注意的是，球形胶束保持形状可转化性。在循环和分布后，它们响应于650 nm激光照射，并在形态上改变为纳米纤维，从而促进它们在肿瘤内的显著保留。在用硫代缩酮接头（PTX 2-TK）负载活性氧物质响应性紫杉醇二聚体后，所得PTX 2-TK @ Ce 6/BR-FFVLK-PEG纳米药物用作用于癌症治疗的有效化学-光动力治疗剂。在细胞水平和动物水平的评估显示，PTX 2-TK@Ce6/BR-FFVLK-PEG具有上级的生物相容性和生物分布，并且在静脉注射的共同剂量（10 mg kg（-1）PTX和3.3 mg kg（-1）Ce 6）下抑制82.6%的体外细胞生长和61.8%的体内肿瘤生长，成为在癌症治疗中具有非凡潜力的新型纳米药物。
Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe-Phe-Val-Leu-Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR-FFVLK-PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species-responsive paclitaxel dimer with thioketal linker (PTX2-TK), the resultant PTX2-TK@Ce6/BR-FFVLK-PEG nanomedicine serves as a potent chemo-photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX2-TK@Ce6/BR-FFVLK-PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg(-1) PTX and 3.3 mg kg(-1) Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.