Bio-Organic Chemistry, Institute for Complex Molecular Systems, Institution, Eindhoven University of Technology, P.O. Box 513 (STO 3.41), 5600 MB, Eindhoven, the Netherlands.
Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China.
Small. 2019 Sep;15(38):e1901849. doi: 10.1002/smll.201901849. Epub 2019 Aug 5.
Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.
用精确的形态特征工程设计可生物降解的纳米结构是纳米医学的一个关键目标。特别是，由于形状在生物医学环境中的有利影响，不对称（即非球形）纳米颗粒是理想的。通过分子工程，可以将独特的形态特征编程到嵌段共聚物（BCP）的自组装中。然而，由于非降解成分的普遍性以及制造过程中使用有毒溶剂，生物相容性和可扩展性的标准限制了进展。为了解决这一不足，已经开发出一种制造形态不对称纳米蠕虫的稳健策略，该策略由可生物降解的 BCP 组成。由聚乙二醇嵌段聚（己内酯梯度-三亚甲基碳酸酯）（PEG-PCLgTMC）组成的模块化 BCP，具有季铵-TMC（PTMC-Q）末端链，通过直接水合作用自组装成具有良好定义的纳米结构。通过在水合过程中控制溶液离子强度，可以将颗粒形态从球形胶束切换到纳米蠕虫（具有不同纵横比的）。这种离子诱导的转变是通过盐屏蔽链间斥力来调节链堆积来驱动的，导致胶束伸长。纳米蠕虫可以高效地装载细胞毒性药物（例如阿霉素），优先与癌细胞相互作用，并增加肿瘤穿透性。这项工作展示了编程 BCP 组装的能力和不对称纳米系统在抗癌药物输送中的潜力。
