pH-Responsive hydrogen-bonded supramolecular micelles, composed of a water-soluble poly(ethylene glycol) polymer with two terminal sextuple hydrogen bonding groups, can spontaneously organize in aqueous media to give well-defined, uniformly sized spherical micelles. The supramolecular micelles exhibit a number of unique physical characteristics, such as interesting amphiphilic behavior, desirable micellar size and nanospherical morphology, excellent biocompatibility, tailorable drug-loading capacities, and high structural stability in media containing serum or red blood cells. In addition, the drug release kinetics of drug-loaded micelles can be easily manipulated to achieve the desired release profile by regulating the environmental pH, thus these micelles are highly attractive candidates as an intelligent drug carrier system for cancer therapy. Cytotoxicity assays showed that the drug-loaded micelles induced pH-dependent intracellular drug release and exerted strong antiproliferative and cytotoxic activities toward cancer cells. Importantly, cellular uptake and flow cytometric analyses confirmed that a mildly acidic intracellular environment significantly increased cellular internalization of the drug-loaded micelles and subsequent drug release in the cytoplasm and nucleus of cancer cells, resulting in more effective induction of apoptotic cell death. Thus, this system may provide an efficient route toward achieving the fundamental properties and practical realization of pH-sensitive drug-delivery systems for chemotherapy.

中文翻译：

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具有pH响应特性的自组装超分子胶束，用于更有效的癌症化学治疗

pH响应型氢键超分子胶束由具有两个末端六元氢键基团的水溶性聚（乙二醇）聚合物组成，可在水性介质中自发组织，从而形成轮廓分明，大小均一的球形胶束。超分子胶束表现出许多独特的物理特性，例如有趣的两亲行为，理想的胶束大小和纳米球形形态，出色的生物相容性，可调节的载药量以及在含有血清或红细胞的培养基中的高结构稳定性。另外，可通过调节环境pH值轻松控制载药胶束的药物释放动力学，以实现所需的释放曲线，因此，这些胶束作为用于癌症治疗的智能药物载体系统非常有吸引力。细胞毒性试验表明，载药的胶束可诱导pH依赖性细胞内药物释放，并对癌细胞具有强大的抗增殖和细胞毒活性。重要的是，细胞摄取和流式细胞仪分析证实，弱酸性细胞内环境显着增加了载药胶束的细胞内在化和随后在癌细胞的细胞质和细胞核中的药物释放，从而导致更有效地诱导凋亡细胞死亡。因此，该系统可为实现用于化学疗法的pH敏感药物递送系统的基本性质和实际实现提供有效途径。