International Journal of Nanomedicine (Nov 2023)
Preparation and Characterization Evaluation of Poly(L-Glutamic Acid)-g-Methoxy Poly(Ethylene Glycol)/Combretastatin A4/BLZ945 Nanoparticles for Cervical Cancer Therapy
Abstract
Dongmei Guo,1 Yue Huang,2 Kun Wang,2 Chenguang Yang,2 Lili Ma,2 Yu Zhang,2 Haiyang Yu,2 Manhua Cui,1 Zhaohui Tang2 1Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin Province, 130041, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Manhua Cui, Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin Province, 130041, People’s Republic of China, Email [email protected] Yue Huang, Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China, Tel/Fax +86 431 85262116, Email [email protected]: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy.Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials. Keywords: combretastatin A4, BLZ945, glutamic acid, nano character, cervical cancer