Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.
Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.
复制标题
超分子聚乙二醇化树突系统作为 pH/氧化还原双响应治疗诊断纳米平台，用于铂药物输送和近红外成像
作者：
Li Y;Li Y;Zhang X;Xu X;Zhang Z;Hu C;He Y;Gu Z
最近，自组装小树突状分子形成超分子树突状系统为开发生物医学应用的多功能纳米平台提供了另一种策略。我们在此报道了一种双响应的超分子聚乙二醇树突状系统，用于高效的铂基药物递送和近红外（NIR）跟踪。通过精细的分子/超分子工程，通过生物可还原二硫键稳定超分子树突状体系，并赋予近红外荧光探针，将聚乙二醇化铂衍生物配位到超分子树突状模板丰富的外周基团上，生成pH/氧化还原双响应的治疗性超分子聚乙二醇化树突状体系（tspds）。由于其稳定的纳米结构和聚乙二醇化的外壳在血液循环中的作用，tspds显著改善了铂类药物的药代动力学和生物分布。肿瘤细胞内环境（低pH和高谷胱甘肽浓度）通过酸不稳定的配位键和氧化还原-可切割的二硫键触发tspds快速分解，然后铂类药物被递送到细胞核中发挥抗肿瘤活性。体内抗肿瘤实验表明，tspds不仅具有与临床顺铂相当的高抗肿瘤效率，而且还能降低铂类药物的肾毒性。此外，tspds的近红外荧光成功地显示了纳米平台的体外和体内命运，揭示了细胞内铂的传递和药代动力学。这些结果证实了具有复杂纳米结构和优异性能的定制超分子树突系统是一种有希望作为智能治疗纳米平台的候选材料。
Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.