HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model

Gou, Yi1,2; Zhang, Zhenlei1; Li, Dongyang3; Zhao, Lei1; Cai, Meiling1; Sun, Zhewen1; Li, Yongping1; Zhang, Yao1; Khan, Hamid1; Sun, Hongbing1,4; Wang, Tao3; Liang, Hong1; Yang, Feng1

2018-01-19

10.1080/10717544.2018.1428245

DRUG DELIVERY   影响因子和分区

1071-7544

1521-0464

Multi-drug delivery systems, which may be promising solution to overcome obstacles, have limited the clinical success of multi-drug combination therapies to treat cancer. To this end, we used three different anticancer agents, Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)-based multi-drug delivery systems in a breast cancer model to investigate the therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells in vivo, and to regulate the drugs' release from HSA. The HSA complex structure revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N-donor residue replacing a leaving group and coordinating to their metal centers, respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release behavior of three agents form HSA can be regulated at different pH levels. Importantly, in vivo results revealed that the HSA-NAMI-A-Cu(BpT)Br-DOX complex not only increases the targeting ability compared with a combination of the three agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance to drug-resistant breast cancer cell lines.

Albumin combination therapy drug delivery systems drug release drug resistant

SCI

英语

通讯

Ministry of Education of China[CMEMR2017-A03]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000423538600002

TAYLOR & FRANCIS LTD

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Guangxi Normal Univ, Minist Sci & Technol China, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Rd, Guilin 541004, Guangxi, Peoples R China
2.Nantong Univ, Sch Pharm, Nantong, Jiangsu, Peoples R China
3.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Guangdong, Peoples R China
4.China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing, Jiangsu, Peoples R China

Gou, Yi,Zhang, Zhenlei,Li, Dongyang,et al. HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model[J]. DRUG DELIVERY,2018,25(1):321-329.

Gou, Yi.,Zhang, Zhenlei.,Li, Dongyang.,Zhao, Lei.,Cai, Meiling.,...&Yang, Feng.(2018).HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model.DRUG DELIVERY,25(1),321-329.

Gou, Yi,et al."HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model".DRUG DELIVERY 25.1(2018):321-329.