College of Pharmaceutical Sciences, Hangzhou(China), 866 Yuhangtang Road, Hangzhou 310058 (China).
Angew Chem Int Ed Engl. 2015 Mar 2;54(10):3126-31. doi: 10.1002/anie.201411524. Epub 2015 Jan 28.
Thermally sensitive polymeric nanocarriers were developed to optimize the release profile of encapsulated compounds to improve treatment efficiency. However, when referring to thermally sensitive polymeric nanocarriers, this usually means systems fabricated from lower critical solution temperature (LCST) polymers, which have been intensively studied. To extend the field of thermally sensitive polymeric nanocarriers, we for the first time fabricated a polymeric drug delivery system having an upper critical solution temperature (UCST) of 43 °C based on an amphiphilic polymer poly(AAm-co-AN)-g-PEG. The resulting polymeric micelles could effectively encapsulate doxorubicin and exhibited thermally sensitive drug release both in vitro and in vivo. A drastically improved anticancer efficiency (IC50 decreased from 4.6 to 1.6 μg mL(-1), tumor inhibition rate increased from 55.6% to 92.8%) was observed. These results suggest that UCST-based drug delivery can be an alternative to thermally sensitive LCST-based drug delivery systems for an enhanced antitumor efficiency.
我们研发了对温度敏感的聚合纳米载体，以优化包封化合物的释放曲线，从而提高治疗效果。然而，当提到对温度敏感的聚合纳米载体时，通常是指由低临界溶液温度（LCST）聚合物制成的系统，这些系统已经得到了深入研究。为了拓展对温度敏感的聚合纳米载体的研究领域，我们首次构建了一种具有 43°C 上临界溶液温度（UCST）的基于两亲性聚合物聚（AAm-co-AN）-g-PEG 的聚合物药物传递系统。所得的聚合物胶束可以有效地包封阿霉素，并在体外和体内表现出对温度敏感的药物释放。观察到抗癌效率得到了显著提高（IC50 从 4.6μg/mL 降低至 1.6μg/mL，肿瘤抑制率从 55.6%增加至 92.8%）。这些结果表明，基于 UCST 的药物传递可以作为提高抗肿瘤效率的替代方法，替代基于 LCST 的热敏药物传递系统。
