Tailor-Made Dual pH-Sensitive Polymer-Doxorubicin Nanoparticles for Efficient Anticancer Drug Delivery
Tailor-Made Dual pH-Sensitive Polymer-Doxorubicin Nanoparticles for Efficient Anticancer Drug Delivery
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用于高效抗癌药物输送的定制双 pH 敏感聚合物-阿霉素纳米颗粒
DOI：
10.1021/ja207150n
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发表时间：
2011-11-09
影响因子：
15
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Du, Jin-Zhi;Du, Xiao-Jiao;Wang, Jun
由于耐药性和无效的细胞摄取，将治疗剂有效递送到肿瘤细胞中以增加细胞内药物浓度是癌症治疗的主要挑战。在此，我们设计了一种量身定制的双重pH敏感的聚合物药物缀合物纳米颗粒系统来克服这些挑战。纳米颗粒能够在肿瘤细胞外pH（类似于6.8）下将其表面电荷从负逆转为正，以促进细胞内化。随后，亚细胞区室如内体（类似于5.0）中显著增加的酸度进一步促进多柔比星从内吞的药物载体中释放。这种双重pH敏感的纳米颗粒在耐药癌症干细胞中表现出增强的细胞毒性，表明其在癌症治疗方面具有巨大潜力。
Efficient delivery of therapeutics into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to drug resistance and inefficient cellular uptake. Herein, we have designed a tailor-made dual pH-sensitive polymer drug conjugate nanoparticulate system to overcome the challenges. The nanoparticle is capable of reversing its surface charge from negative to positive at tumor extracellular pH (similar to 6.8) to facilitate cell internalization. Subsequently, the significantly increased acidity in subcellular compartments such as the endosome (similar to 5.0) further promotes doxorubicin release from the endocytosed drug carriers. This dual pH-sensitive nanoparticle has showed enhanced cytotoxicity in drug-resistant cancer stem cells, indicating its great potential for cancer therapy.