Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression.
Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression.
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作者：
Liu G;Tsai HI;Zeng X;Zuo Y;Tao W;Han J;Mei L
有效地将抗癌药物输送到肿瘤组织中以提高治疗效果仍然是一个迫切的需求。为了满足这一需求，开发了一种基于隐形纳米胶囊的药物释放系统。这种纳米胶囊是通过在蛋白质牛血清白蛋白(BSA)周围包裹隐形交联的聚(2-甲基丙烯酰氧乙基磷酰胆碱)(PMPC)和苯甲醛基团，然后通过pH响应的苯甲酰亚胺键与阿霉素(Dox)连接而成的。体外实验结果表明，在酸性肿瘤微环境(pH~6.5)下，Dox偶联纳米胶囊(nBSA-Dox)能有效地释放药物，对人肝癌细胞有杀伤作用。NBSA-Dox在小鼠体内的半衰期显著延长，其血浆Dox的曲线下面积是游离Dox的242倍。体内实验结果证实，该纳米胶囊在肿瘤组织中有效积聚，并显著抑制肿瘤生长。
The efficient delivery of anticancer drugs into tumor tissues to improve therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug delivery system based on a stealthy nanocapsule was developed. This nanocapsule was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH-responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment (pH ~6.5) and killed HepG2 human liver cancer cells. The half-life of Dox conjugated to nBSA in mice was significantly prolonged, and the area-under-curve of plasma Dox of the mice treated with nBSA-Dox was as much as 242 fold of free Dox. The in vivo results confirmed that this nanocapsule efficiently accumulated in tumor tissue and significantly suppressed the tumor growth.