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

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

doi:10.3389/fbioe.2024.1336692

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

Front Bioeng Biotechnol. 2024 Feb 5:12:1336692. doi: 10.3389/fbioe.2024.1336692. eCollection 2024.

Authors

Jiaqi Chen¹, Min Yin¹, Chenguang Yang², Kun Wang², Lili Ma², Haiyang Yu², Yue Huang², Feng Liu¹, Zhaohui Tang²

Affiliations

¹ Department of Nephrology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.

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.

Keywords: BLZ945; Renca renal carcinoma; combretastatin A4; mechanism; therapeutic effect.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (Projects 52103195) and Jilin Scientific and Technological Development Program (grant number YDZJ202301ZYTS018).