药学学报, 2009, 44(12): 1328-1335
引用本文:
许金霞 唐建斌 赵鲁杭 申有青. 肿瘤pH响应的聚合物胶束用于肿瘤药物靶向输送的研究进展[J]. 药学学报, 2009, 44(12): 1328-1335.
HU Jin-Xia, Tang-Jian-Bin, Diao-Lu-Hang, Shen-Wei-Jing. Advances in the study of tumor pH-responsive polymeric micelles for cancer drug targeting delivery[J]. Acta Pharmaceutica Sinica, 2009, 44(12): 1328-1335.

肿瘤pH响应的聚合物胶束用于肿瘤药物靶向输送的研究进展
许金霞1, 唐建斌2, 赵鲁杭1*, 申有青2*?
(1. 浙江大学医学院生化与遗传系, 浙江 杭州 310058; 2. 浙江大学化学工程与生物工程系, 浙江 杭州 310027)
摘要:

本文综述了肿瘤pH响应的聚合物胶束 (pH-responsive polymeric micelles) 靶向输送抗癌药物的研究进展。肿瘤组织的细胞间质呈弱酸性 (pH < 7), 而肿瘤细胞内的内涵体和溶酶体具有更强的酸性 (pH 46)pH响应的聚合物胶束的内核或外壳在肿瘤酸性pH下能发生质子化或快速化学反应, 导致其物理性能发生改变。胶束对肿瘤酸性pH的响应功能可以用来实现药物的快速释放、激活胶束的靶向功能、促进胶束的细胞内吞, 以及促使胶束从溶酶体逃逸到细胞质溶质 (cytosol) , 并靶向细胞核等细胞器。大量的体内和体外实验表明, pH响应型胶束输送抗癌药物可以明显增加药物在作用部位如细胞质和细胞核中的浓度, 饱和癌细胞的多种抗药机制, 从而克服肿瘤细胞的耐药性, 提高抗癌药物的治疗效率并减少其毒副作用。

关键词:   
Advances in the study of tumor pH-responsive polymeric micelles for cancer drug targeting delivery
Abstract:

This review presents the state of the art of pH-responsive polymeric micelles for cancer drug   delivery.  Solid tumors have a weakly acidic extracellular pH (pH < 7), and cancer cells have even more acidic pH in endosomes and lysosomes (pH 4−6).  The pH-gradients in tumor can be explored for tumor targeting and drug release in cancer drug delivery by applying pH-responsive polymeric micelles.  The pH-responsive   polymeric micelles consist of a corona and a core, and are made of amphiphilic copolymers, in which there are pH-responsive polymeric blocks.  Two types of pH-responsive polymers-protonizable polymers and acid-labile polymers have been mainly used to make pH-responsive micelles for drug delivery.  The protonizable polymers are polybases or polyacids, and their water-soluble/insoluble or charge states undergo changes with the protonation or deprotonation stimulated by external acidity, while the acid-labile polymers change their physical properties by chemical reaction stimulated by the acidity.  Polymeric micelles whose core or coronas respond to the tumor extracellular acidity can be explored for triggering the fast release of the carried drug, activating the targeting group and accelerating the endocytosis of drug-loaded polymeric micelles, and those whose core or coronas   respond to the tumor lysosomal acidity can be used for facilitating their escape from the lysosomes and targeting the nucleus.  Various in vivo and in vitro experiments demonstrated that pH-responsive polymeric micelles are effective for cellular targeting, internalization, fast drug release and nuclear localization, and hence enhancing the therapeutic efficacy and reducing the side effect of cancer chemical therapy.

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