Self-Assembly Behavior and Cytotoxicity of PEG-b-PLA Nanoparticles for Improved Oxaliplatin Delivery: Effect of PLA Block Length

Y. Puchkova, N. Sedush, E. Kuznetsova, A. Nazarov, S. Chvalun
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Abstract

The present study investigates the effect of the length of the hydrophobic poly(D,L-lactide) block on the self-assembly behavior of amphiphilic poly(D,L-lactide)-b-poly(ethylene glycol) (P(D,L)LA-b-PEG5k) copolymers with a large variation in molecular weight of the hydrophobic block (ranging from 5 to 100 kDa). To evaluate the cytotoxic effect of oxaliplatin-loaded P(D,L)LA-b-PEG5k nanoparticles (OXA-NPs) prepared by the nanoprecipitation method, a half maximal inhibitory concentration (IC50) study was conducted in cancer cell lines (MCF7, HCT116, and A549). The assays revealed that the IC50 values for OXA-NPs in HCT116 (1.93 ± 0.08 nM) and A549 (2.84 ± 0.11 nM) were significantly lower than those of pure OXA (12.70 ± 1.14 and 29.30 ± 0.40 nM, respectively). Moreover, the results showed that normal fibroblasts treated with blank NPs exhibited no significant growth inhibition in the concentration range of 0.001–1 mg mL–1, indicating their high biocompatibility.

Abstract Image

用于改善奥沙利铂递送的PEG-b-PLA纳米颗粒的自组装行为和细胞毒性:PLA块长度的影响
摘要本文研究了疏水聚(D,L-丙交酯)嵌段长度对两亲性聚(D,L-丙交酯)-b-聚乙二醇(P(D,L)LA-b-PEG5k)共聚物自组装行为的影响,其疏水嵌段分子量变化较大(5 ~ 100 kDa)。为了评价纳米沉淀法制备的奥沙利铂载P(D,L)LA-b-PEG5k纳米颗粒(OXA-NPs)的细胞毒作用,我们对MCF7、HCT116和A549癌细胞进行了半最大抑制浓度(IC50)研究。结果表明,OXA- nps在HCT116(1.93±0.08 nM)和A549(2.84±0.11 nM)中的IC50值明显低于纯OXA(分别为12.70±1.14和29.30±0.40 nM)。此外,空白NPs在0.001-1 mg mL-1浓度范围内对正常成纤维细胞无明显的生长抑制作用,表明其具有较高的生物相容性。
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