Abstract

The purpose of this study was to develop a novel drug-polymer conjugation (mPEG-b-PCL-DOX) and study on its toxicity, bio-safety, and in vitro antitumor activity of mPEG-b-PCL-DOX. The polymer methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL) was prepared by ring-opening polymerization. Then, succinic anhydride was reacted with mPEG-b-PCL via esterification reaction to produce mPEG-b-PCL-COOH. Finally, the polymer mPEG-b-PCL-DOX was obtained by conjugating DOX to mPEG-b-PCL-COOH by amidation. The Fourier transform infrared spectroscopy (FTIR) and ¹H nuclear magnetic resonance (¹H NMR) spectra were used to study the structures of obtained polymers. Transmission electron microscope (TEM) and Dynamic laser scattering (DLS) were employed to monitor the morphology and size distribution of mPEG-b-PCL-DOX nanoparticles (NPs). The mPEG-b-PCL-DOX NPs were administrated to KM rats by intraperitoneal injection to study the bio-safety of final NPs. The cell uptake and in vitro anti-tumor activity of final NPs were carried out with HCT116 cells as models. FTIR and ¹H NMR spectra confirmed the obtaining of mPEG-b-PCL-DOX. The fabricated NPs were in round shapes with an average diameter of 300 nm. These NPs did not induce hemolysis and physiological or pathological changes in rats’s organs. Finally, cell teats showed that these NPs could be endocytosed by HCT 116 cells, and they had better anti-tumor effects than free DOX did. Therefore, the mPEG-b-PCL-DOX NPs had a potential application in anti-cancer therapy.

摘要

本研究的目的是开发一种新的药物-聚合物偶联物 ( mPEG- b -PCL-DOX) 并研究其毒性、生物安全性和mPEG- b -PCL-DOX 的体外抗肿瘤活性。聚合物甲氧基聚(乙二醇)-嵌段-聚(ε-己内酯)( mPEG - b- PCL)通过开环聚合制备。然后，琥珀酸酐与反应的mPEG- b -PCL经由酯化反应产生的mPEG- b -PCL-COOH。最后，通过酰胺化将DOX 与mPEG- b -PCL-COOH共轭得到聚合物mPEG- b -PCL-DOX 。傅里叶变换红外光谱 (FTIR) 和¹使用 H 核磁共振 ( ¹ H NMR) 光谱来研究所得聚合物的结构。采用透射电子显微镜 (TEM) 和动态激光散射 (DLS) 来监测mPEG- b -PCL-DOX 纳米粒子 (NP)的形态和尺寸分布。该的mPEG- b -PCL-DOX纳米粒腹腔注射给药，以KM大鼠学习最终NP的生物安全性。最终NPs的细胞摄取和体外抗肿瘤活性以HCT116细胞为模型进行。FTIR 和¹ H NMR 光谱证实了 mPEG- b的获得-PCL-DOX。制造的纳米颗粒呈圆形，平均直径为 300 nm。这些纳米颗粒不会引起大鼠器官的溶血和生理或病理变化。最后，细胞乳头显示这些 NPs 可以被 HCT 116 细胞内吞，并且它们比游离 DOX 具有更好的抗肿瘤作用。因此，mPEG- b -PCL-DOX NPs 在抗癌治疗中具有潜在的应用价值。