Qian Yun, Zhang Jun, Xu Rui, Li Qiang, Shen Qi, Zhu Guofu
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Int J Biol Macromol. 2021 Jul 31;183:2215-2226. doi: 10.1016/j.ijbiomac.2021.05.204. Epub 2021 Jun 9.
Triple negative breast cancer (TNBC) metastasis is still one of the obstacles in clinical treatment, while highly-effective cancer drugs usually cannot be used for their hydrophobicity and comprehensive system toxicity. This study built a kind of pH-sensitive nanoparticles (PP/H NPs) constructed by poly (lactic-co-glycolic acid) modified with β-cyclodextrin (PLGA-β-CD), polyethyleneimine grafted with benzimidazole (PEI-BM) and low molecular weight heparin (LMWH) to delivery Celastrol (Cela) and ferrocene (Fc) for breast cancer therapy. PLGA-β-CD and PEI-BM were synthesized by amidation reaction, the amphipathic polymer nanoparticles with 108.37 ± 1.02 nm were self-assembled in water. After PP/H NPs treatment, the half maximal inhibitory concentration (IC) decreased by 91% compared with Cela, and ROS level was also elevated. PP/H NPs led to substantial tumor inhibiting rate (TIR, 65.86%), utilized LMWH to strengthen the anti-metastasis effect of PP/H NPs. PP/H NPs took advantage of exogenous chemotherapeutics and endogenous ROS to inhibit tumor growth, and combined with LMWH to hinder breast cancer metastasis.
三阴性乳腺癌（TNBC）转移仍是临床治疗中的障碍之一，而高效抗癌药物通常因其疏水性和综合系统毒性而无法使用。本研究构建了一种由β-环糊精修饰的聚（乳酸-乙醇酸）（PLGA-β-CD）、接枝苯并咪唑的聚乙烯亚胺（PEI-BM）和低分子量肝素（LMWH）构建的pH敏感纳米颗粒（PP/H NPs），用于递送雷公藤红素（Cela）和二茂铁（Fc）以治疗乳腺癌。PLGA-β-CD和PEI-BM通过酰胺化反应合成，两亲性聚合物纳米颗粒在水中自组装，粒径为108.37±1.02nm。PP/H NPs处理后，半数最大抑制浓度（IC）与Cela相比降低了91%，活性氧水平也有所升高。PP/H NPs导致显著的肿瘤抑制率（TIR，65.86%），利用LMWH增强PP/H NPs的抗转移作用。PP/H NPs利用外源性化疗药物和内源性活性氧抑制肿瘤生长，并与LMWH联合阻碍乳腺癌转移。
