Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan.
Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan.
Macromol Biosci. 2020 Dec;20(12):e2000233. doi: 10.1002/mabi.202000233. Epub 2020 Sep 1.
Functional supramolecular micelles containing self-complementary multiple hydrogen bonding adenine groups (A-PPG) can spontaneously self-assemble into stable nanosized micelles in aqueous solution. These micelles can be used to selectively deliver anticancer drugs to cancer cells and effectively promote tumor cell death via apoptosis, without harming normal cells. The drug-loaded micelles exhibit tunable drug-loading capacity and rapid pH-triggered drug release under acidic conditions, as well as a high drug-entrapment stability in serum-rich media due to the reversible hydrogen-bonded adenine-adenine interactions within the micellar interior; these properties are critical to achieving effective chemotherapeutic drug delivery and controlled drug release. In vitro assays show that the drug-loaded micelles exert significant cytotoxic effects on cancer cells, with minimal effects on normal cells under physiological conditions. Cytotoxicity assays using A-PPG micelles loaded with different anticancer drugs confirm these effects. Importantly, cellular internalization and flow cytometric analyses demonstrate that the adenine moieties within A-PPG micelles significantly increase selective endocytic uptake of the supramolecular micelles by cancer cells, which in turn induce apoptotic cell death and substantially enhance the response to chemotherapy. Thus, A-PPG micelles can improve the safety and efficacy of cancer chemotherapy.
含有自互补多重氢键腺嘌呤基团（A-PPG）的功能超分子胶束可以在水溶液中自发组装成稳定的纳米级胶束。这些胶束可以用于选择性地将抗癌药物递送到癌细胞中，并通过细胞凋亡有效地促进肿瘤细胞死亡，而不会伤害正常细胞。载药胶束在酸性条件下具有可调的载药能力和快速的 pH 触发药物释放，并且由于胶束内部的可逆氢键腺嘌呤-腺嘌呤相互作用，在富含血清的介质中具有高的药物包封稳定性；这些特性对于实现有效的化学治疗药物递送和控制药物释放至关重要。体外实验表明，载药胶束对癌细胞具有显著的细胞毒性作用，在生理条件下对正常细胞的影响最小。使用载有不同抗癌药物的 A-PPG 胶束进行的细胞毒性实验证实了这些效果。重要的是，细胞内化和流式细胞术分析表明，A-PPG 胶束中的腺嘌呤部分显著增加了癌细胞对超分子胶束的选择性内吞摄取，进而诱导细胞凋亡并显著增强对化疗的反应。因此，A-PPG 胶束可以提高癌症化疗的安全性和疗效。
