TPGS functionalized mesoporous silica nanoparticles for anticancer drug delivery to overcome multidrug resistance

被引：41

作者：

Zhao, Peiqi ^{[1
]}

Li, Lanfang ^{[1
]}

Zhou, Shiyong ^{[1
]}

Qiu, Lihua ^{[1
]}

Qian, Zhengzi ^{[1
]}

Liu, Xianming ^{[1
]}

Cao, Xuchen ^{[2
]}

Zhang, Huilai ^{[1
]}

机构：

[1] Tianjin Med Univ, Dept Lymphoma,SinoUS Ctr Lymphoma & Leukemia, Tianjin Med Univ Canc Inst & Hosp,Tianjins Clin R, Natl Clin Res Ctr Canc,Key Lab Canc Prevent & The, Tianjin 300060, Peoples R China

[2] Tianjin Med Univ, Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc,Minist Educ, Key Lab Canc Prevent & Therapy,Key Lab Breast Can, Tianjin 300060, Peoples R China

来源：

MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2018年 / 84卷

基金：

中国国家自然科学基金;

关键词：

TPGS; P-gp inhibition; Multidrug resistance; Mesoporous silica nanoparticles (MSNs); Doxorubicin; UP-CONVERSION NANOPARTICLES; RESPONSIVE NANOPARTICLES; P-GLYCOPROTEIN; IN-VITRO; CANCER; DOXORUBICIN; NANOCARRIERS; INHIBITION; REVERSAL; SYSTEM;

D O I：

10.1016/j.msec.2017.11.040

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

Multidrug resistance (MDR) has become a very serious problem in cancer therapy. To effectively reverse MDR in tumor treatments, a new pH-sensitive nano drug delivery system (NDDS) composed of mesoporous silica nanoparticles (MSNs) and D-a-tocopheryl poly-ethylene glycol 1000 succinate (TPGS) copolymers was synthesized to deliver doxorubicin (DOX) into drug-resistant breast cancer cell line (MCF-7/ADR). DOX@MSNs-TPGS were characterized to have a single peak size distribution, high DOX loading efficiency and a pH-dependent drug release profile. MSNs-TPGS were internalized via caveolae, clathrin-mediated endocytosis and energy-dependent cellular uptake. The DOX@MSNs-TPGS exhibited 10-fold enhanced cell killing potency compared to free DOX and DOX@MSNs. The enhanced MDR reversal effect was ascribed to the higher amount of cellular uptake of DOX@MSNs-TPGS in MCF-7/ADR cells than that of free DOX and DOX@MSNs, as a result of the inhibition of P-gp mediated drug efflux by TPGS. In vivo studies of NDDS in tumor-bearing mice showed that DOX@MSNs-TPGS displayed better efficacy against MDR tumors in mice and reached the tumor site more effectively than DOX and DOX@MSNs, with minimal toxicity. These results suggest DOX@MSNs-TPGS developed in this study have promising applications to overcome drug resistance in tumor treatments.

引用

页码：108 / 117

页数：10

共 49 条

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