M1 Macrophage-Biomimetic Targeted Nanoparticles Containing Oxygen Self-Supplied Enzyme for Enhancing the Chemotherapy

化学 巨噬细胞 纳米颗粒 体外 纳米技术 化疗 癌症研究 生物化学 材料科学 医学 内科学
作者
Jiayi Zhang,Bing Gu,Shimiao Wu,Lin Liu,Ying Gao,Yucen Yao,Degong Yang,Juan Du,Chunrong Yang
出处
期刊:Pharmaceutics [MDPI AG]
卷期号:15 (9): 2243-2243 被引量:5
标识
DOI:10.3390/pharmaceutics15092243
摘要

Tumor hypoxia is considered one of the key causes of the ineffectiveness of various strategies for cancer treatment, and the non-specific effects of chemotherapy drugs on tumor treatment often lead to systemic toxicity. Thus, we designed M1 macrophage-biomimetic-targeted nanoparticles (DOX/CAT@PLGA-M1) which contain oxygen self-supplied enzyme (catalase, CAT) and chemo-therapeutic drug (doxorubicin, DOX). The particle size of DOX/CAT@PLGA-M1 was 202.32 ± 2.27 nm (PDI < 0.3). DOX/CAT@PLGA-M1 exhibited a characteristic core-shell bilayer membrane structure. The CAT activity of DOX/CAT@PLGA-M1 was 1000 (U/mL), which indicated that the formation of NPs did not significantly affect its enzymatic activity. And in vitro drug release showed that the cumulative release rate of DOX/CAT@PLGA-M1 was enhanced from 26.93% to 50.10% in the release medium of hydrogen peroxide, which was attributed to the reaction of CAT in the NPs. DOX/CAT@PLGA-M1 displayed a significantly higher uptake in 4T1 cells, because VCAM-1 in tumor cells interacted with specific integrin (α4 and β1), and thereby achieved tumor sites. And the tumor volume of the DOX/CAT@PLGA-M1 group was significantly reduced (0.22 cm3), which further proved the active targeting effect of the M1 macrophage membrane. Above all, a novel multifunctional nano-therapy was developed which improved tumor hypoxia and obtained tumor targeting activity.
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