National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
Theranostics. 2016 Jun 5;6(9):1293-305. doi: 10.7150/thno.15081. eCollection 2016.
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.
最近，自组装小分子树状大分子成超分子树状体系为开发用于生物医学应用的多功能纳米平台提供了一种替代策略。本文报道了一种双响应超分子聚乙二醇化树状体系，用于高效递送电镜检查药物和近红外（NIR）跟踪。通过精细的分子/超分子工程，超分子树状体系通过生物还原二硫键稳定，并赋予近红外荧光探针，并将聚乙二醇化的铂衍生物配位到超分子树状模板的丰富外围基团上，生成 pH/氧化还原双响应治疗性超分子聚乙二醇化树状体系（TSPDSs）。由于 TSPDSs 在血液循环过程中具有稳定的纳米结构和聚乙二醇化外壳，因此显著改善了基于铂的药物的药代动力学和生物分布。肿瘤细胞内环境（低 pH 值和高谷胱甘肽浓度）可由于酸不稳定的配位键和氧化还原可裂解的二硫键引发 TSPDSs 的快速崩解，然后将基于铂的药物递送至细胞核以发挥抗肿瘤活性。体内抗肿瘤治疗表明，TSPDSs 不仅提供了与临床顺铂相当的高抗肿瘤效率，而且还降低了基于铂的药物的肾毒性。此外，TSPDSs 的近红外荧光成功地在体外和体内可视化了纳米平台的命运，并揭示了细胞内铂的递送和药代动力学。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状体系是一种很有前途的智能治疗性纳米平台候选物。
