Circulation stability in vivo and stimuli-responsiveness under a tumor microenvironment of the polymeric prodrug micellar drug delivery systems are very critical to improve the tumor therapeutic efficiency. In this study, a series of polyamidoamine (PAMAM)-graft-poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA)-block-poly(betaine sulfonate) (PSBMA) (PDS) unimolecular micelles were prepared via atom transfer radical polymerization. PAMAM served as a hydrophobic core to load the drug, the PDMAEMA segment was a middle layer to provide both thermo- and pH-sensitivity, whereas the PSMBA shell layer was used to improve the stability of the unimolecular micelles. The PDS exhibited a spherical structure with the size of 10–20 nm at pH 7.4. PDS micelles had excellent stability to resist the large volume liquid dilution. Moreover, it exhibited excellent stability in a complex biological microenvironment because of a superhigh antiprotein adhesion capacity of the PSBMA shell layer compared with PAMAM micelles. Drug release studies confirmed that the DOX can remain in the PDS micelles at pH 7.4 and 37 °C, whereas it can rapidly be released when the pH decreases to 5.0 and/or the temperature increases to 40 °C. In vitro studies suggested that the PDS drug delivery system can effectivity induce apoptosis and inhibit the proliferation of cancer cells. In vivo studies suggested that the PDS micelles prolonged the circulation time, decreased the side effects, and increased the antitumor efficacy. Therefore, the prepared PDS micelles are a potential anticancer drug delivery carrier for cancer therapy.

中文翻译：

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具有pH和温度响应的两性离子单分子胶束：增强的体内循环稳定性和肿瘤治疗效率。

聚合物前药胶束药物递送系统在肿瘤微环境下的体内循环稳定性和刺激反应性对于提高肿瘤治疗效率非常关键。在这项研究中，一系列聚酰胺胺（PAMAM） -接枝-聚（2-（二乙氨基）乙基甲基丙烯酸酯）（PDEAEMA） -块-聚（甜菜碱磺酸盐）（PSBMA）（PDS）中制备的单分子胶束经由原子转移自由基聚合。PAMAM作为疏水性核心负载药物，PDMAEMA段是提供热敏性和pH敏感性的中间层，而PSMBA壳层则用于提高单分子胶束的稳定性。PDS在pH 7.4时呈球形，尺寸为10–20 nm。PDS胶束具有出色的稳定性，可以抵抗大量液体稀释。此外，由于与PSAMA胶束相比，PSBMA壳层具有超高的抗蛋白质粘附能力，因此在复杂的生物微环境中具有极好的稳定性。药物释放研究证实，DOX可以在pH 7.4和37°C时保留在PDS胶束中，而当pH降低到5.0和/或温度升高到40°C时，DOX可以迅速释放。体外研究表明，PDS药物递送系统可以有效诱导凋亡并抑制癌细胞的增殖。体内研究表明，PDS胶束延长了循环时间，减少了副作用，并提高了抗肿瘤功效。因此，制备的PDS胶束是用于癌症治疗的潜在的抗癌药物递送载体。