Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance

被引：94

作者：

Zhao, Yuan ^{[1
]}

Huan, Meng-lei ^{[1
]}

Liu, Miao ^{[1
]}

Cheng, Ying ^{[1
]}

Sun, Yang ^{[2
]}

Cui, Han ^{[1
]}

Liu, Dao-zhou ^{[1
]}

Mei, Qi-bing ^{[2
]}

Zhou, Si-yuan ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, Sch Pharm, Dept Pharmaceut, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Key Lab Gastrointestinal Pharmacol Chinese Med, Xian 710032, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

BREAST-CANCER CELLS; MULTIDRUG-RESISTANCE; DOWN-REGULATION; UP-REGULATION; P-GP; PROTEIN; KINASE; BCL-2; PLGA; PHARMACOKINETICS;

D O I：

10.1038/srep35267

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-kappa B and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.

引用

页数：15

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