Therapeutic effects and underlying mechanism of poly (L-glutamic acid)- g-methoxy poly (ethylene glycol)/combretastatin A4/BLZ945 nanoparticles on Renca renal carcinoma

聚(L-谷氨酸)-γ-甲氧基聚(乙二醇)/康布瑞他汀A4/BLZ945纳米颗粒对肾癌的治疗效果及其潜在机制

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作者:Jiaqi Chen ,Min Yin ,Chenguang Yang ,Kun Wang ,Lili Ma ,Haiyang Yu ,Yue Huang ,Feng Liu ,Zhaohui Tang

Abstract

Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth. Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques. Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages. Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.

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