Tailor-Made pH-Responsive Poly(choline phosphate) Prodrug as a Drug Delivery System for Rapid Cellular Internalization
作者:Wenliang Wang、Bo Wang、Xiaojing Ma、Sanrong Liu、Xudong Shang、Xifei Yu
DOI:10.1021/acs.biomac.6b00455
日期:2016.6.13
Rapid cellular uptake and efficient drug release in tumor cells are two of the major challenges for cancer therapy. Herein, we designed and synthesized a novel pH-responsive polymer–drug conjugate system poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-methoxy-2-oxoethyl methacrylate-hydrazide-doxorubicin) (PCP-Dox) to overcome these two challenges simultaneously. It has been proved that PCP-Dox can be easily and rapidly internalized by various cancer cells due to the strong interaction between multivalent choline phosphate (CP) groups and cell membranes. Furthermore, Dox, linked to the polymer carrier via acid-labile hydrazone bond, can be released from carriers due to the increased acidity in lysosome/endosome (pH 5.0–5.5) after the polymer prodrug was internalized into the cancer cells. The cell viability assay demonstrated that this novel polymer prodrug has shown enhanced cytotoxicity in various cancer cells, indicating its great potential as a new drug delivery system for cancer therapy.
肿瘤细胞对药物的快速吸收和高效释放是癌症治疗面临的两大挑战。在此,我们设计并合成了一种新型 pH 响应聚合物-药物共轭体系聚(2-(甲基丙烯酰氧基)乙基胆碱磷酸酯)-b-聚(2-甲氧基-2-氧代乙基甲基丙烯酸酯-酰肼-多柔比星)(PCP-Dox),以同时克服这两大难题。事实证明,由于多价磷酸胆碱(CP)基团与细胞膜之间的强相互作用,PCP-Dox 可被各种癌细胞轻松、快速地内化。此外,在聚合物原药被癌细胞内化后,由于溶酶体/内质体(pH 值为 5.0-5.5)的酸度增加,通过酸性腙键与聚合物载体相连的 Dox 可以从载体中释放出来。细胞活力测定表明,这种新型聚合物原药对各种癌细胞的细胞毒性都有所增强,这表明它作为一种新的癌症治疗药物递送系统具有巨大的潜力。