Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy
Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy
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PArg修饰的可还原降解聚合物胶束提高抗癌药物递送功效
DOI：
10.1021/acsami.5b10867
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发表时间：
2016-01-27
影响因子：
9.5
通讯作者：
Zhang, Xingdong
中科院分区：
文献类型：
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作者：
Cui, Yani;Sui, Junhui;Zhang, Xingdong
本研究合成了五种具有不同比例亲水性和疏水性片段的可还原降解聚酰胺胺-g-聚乙二醇/聚精氨酸（PAA-g-PEG/PArg）胶束作为新型药物递送载体。聚精氨酸不仅作为亲水片段，还具有细胞穿透功能，可以快速转导到靶细胞中。制备聚酰胺胺-g聚乙二醇（PAA-g-PEG）用于比较。在体外和体内研究了掺入 DOX 的 PAA-g-PEG/PArg 阳离子聚合物胶束的表征和抗肿瘤作用。细胞毒性实验表明PAA-g-PEG/PArg胶束具有良好的生物相容性。与掺入DOX的P.AA-g-PEG胶束相比，掺入DOX的PAA-g-PEG/PArg胶束能够更有效地内化到人肝细胞癌细胞（HepG2）中，并且更快地将DOX释放到细胞质中以抑制细胞增殖。在携带4T1的裸鼠肿瘤模型中，掺入DOX的PAA-gPEG/PArg胶束能够在肿瘤部位有效聚集，并且比PAA-g-PEG胶束具有更长的聚集时间和更显着的聚集浓度。同时，它能很好地抑制实体瘤的生长，延长荷瘤Balb/c小鼠的生存期。这些结果可归因于其适当的纳米尺寸和聚精氨酸作为表面层的细胞穿透特性。 PAA-g-PEG/PArg聚合物胶束作为一种安全、高效的药物递送系统，有望成为一种有前途的递送载体，将疏水性化疗药物靶向肿瘤并显着增强抗肿瘤效果。
In this study, five kinds of reduction-degradable polyamide amine-g-polyethylene glycol/polyarginine (PAA-g-PEG/PArg) micelles with different proportions of hydrophilic and hydrophobic segments were synthesized as novel drug delivery vehicles. Polyarginine not only acted as a hydrophilic segment but also possessed a cell-penetrating function to carry out a rapid transduction into target cells. Polyamide arnine-gpolyethylene glycol (PAA-g-PEG) was prepared for comparison. The characterization and antitumor effect of the DOXincorporated PAA-g-PEG/PArg cationic polymeric micelles were investigated in vitro and in vivo. The cytotoxicity experiments demonstrated that the PAA-g-PEG/PArg micelles have good biocompatibility. Compared with DOX-incorporated P.AA-g-PEG micelles, the DOX-incorporated PAA-g-PEG/PArg micelles were more efficiently internalized into human hepatocellular carcinoma (HepG2) cells and more rapidly released DOX into the cytoplasm to inhibit cell proliferation. In the 4T1-bearing nude mouse tumor models, the DOX-incorporated PAA-gPEG/PArg micelles could efficiently accumulate in the tumor site and had a longer accumulation time and more significant aggregation concentration than those of PAA-g-PEG micelles. Meanwhile, it excellently inhibited the solid tumor growth and extended the survival period of the tumor-bearing Balb/c mice. These results could be attributed to their appropriate nanosize and the cell-penetrating peculiarity of polyarginine as a surface layer. The PAA-g-PEG/PArg polymeric micelles as a safe and high efficiency drug delivery system were expected to be a promising delivery carrier that targeted hydrophobic chemotherapy drugs to tumors and significantly enhanced antitumor effects.