T7 peptide-mediated co-delivery platform overcoming multidrug-resistant breast cancer: In vitro and in vivo evaluation

被引:1
|
作者
Zhang, Shuang-Shuang [1 ,2 ]
Yu, Jia-Hui [1 ]
Jiang, Si -Si [1 ]
Wang, Lun [3 ]
Chen, Jiong [1 ]
Long, Jiao [1 ]
Gu, Shuang-Xi [1 ,2 ]
Li, Hui [4 ]
机构
[1] Wuhan Inst Technol, Sch Chem Engn & Pharm, Wuhan 430205, Hubei, Peoples R China
[2] Wuhan Inst Technol, Pharmaceut Res Inst, Wuhan 430205, Peoples R China
[3] Huazhong Pharmaceut Co Ltd, Xiangyang 441021, Peoples R China
[4] Sichuan Univ, Sch Chem Engn, Chengdu 610065, Peoples R China
基金
中国国家自然科学基金;
关键词
Mutidrug-resistant breast cancer; T7; peptide; Mixed liposomes; Co; -delivery; P-gp inhibitors; SCHISANDRIN-B; P-GLYCOPROTEIN; ENTRAPMENT; EFFICIENCY; SYSTEM;
D O I
10.1016/j.ejpb.2024.114327
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide -modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co -delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug -resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor -targeting capability, and anti -tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co -delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.
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页数:12
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