中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Co-Delivery of Trichosanthin and Albendazole by Nano-Self Assembly for Overcoming Tumor Multidrug-Resistance and Metastasis

文献类型:期刊论文

作者Tang, Yisi1,2; Liang, Jianming2; Wu, Aihua1,2; Chen, Yingzhi2; Zhao, Pengfei2,3; Lin, Tingling2,3; Zhang, Meng2; Xu, Qin1; Wang, Jianxin1; Huang, Yongzhuo2,3
刊名ACS APPLIED MATERIALS & INTERFACES
出版日期2017-08-16
卷号9期号:32页码:26648-26664
关键词Multidrug resistance trichosanthin albendazole albumin nanoparticles silver nanoparticles metastasis
ISSN号1944-8244
DOI10.1021/acsami.7b05292
文献子类Article
英文摘要Multidrug resistance (MDR) and metastasis are the major obstacles in cancer chemotherapy. Nanotechnology-based combination therapy is a useful strategy. Recently, the combination of biologics and small drugs has attracted much attention in cancer therapy. Yet, the treatment outcomes are often compromised by the different pharmacokinetic profiles of the co-administered drugs thus leading to inconsistent drug uptake and suboptimal drug combination at the tumor sites. Nanotechnology-based co-delivery offers a promising method to address this problem, which is well demonstrated in the use of small drug combinations. However, co-delivery of the drugs bearing different physicochemical properties (e.g., proteins and small drugs) remains a formidable challenge. Herein, we developed a self-assembled nanosystem for co-delivery of trichosanthin (TCS) protein and albendazole (ABZ) as a combination therapy for overcoming MDR and metastasis. TCS is a ribosome-inactivating protein with high antitumor activity. However, the druggability of TCS is poor due to its short half-life, lack of tumor specific action, and low cell uptake. ABZ is a clinically used antihelmintic drug, which can also inhibit tubulin polymerization and thus serve as a potential antitumor drug. In our work, ABZ was encapsulated in the albumin-coated silver nanoparticles (termed ABZ@BSA/Ag NP). The thus-formed NPs were negatively charged and could tightly bind with the cationic TCS that was modified with a cell-penetrating peptide (CPP) low-molecular-weight protamine (termed rTL). Via the stable charge interaction, the nanosystem (rTL/ABZ@BSA/Ag NP) was self-assembled, and featured by the TCS corona. The co-delivery system efficiently inhibited the proliferation of the drug-resistant tumor cells (A549/T and HCT8/ADR) by impairing the cytoskeleton, arresting the cell cycle, and enhancing apoptosis. In addition, the migration and invasion of tumor cells were inhibited presumably due to the impeded cytoskeleton functions. The anti-MDR effect was further confirmed by the in vivo studies with the subcutaneous A549/T tumor mouse model. More importantly, the co-delivery system was demonstrated to be able to inhibit metastasis. The co-delivery system of TCS/ABZ provided a potential strategy for both overcoming drug resistance and inhibiting tumor metastasis.
WOS关键词APOPTOTIC CELL-DEATH ; CANCER-CELLS ; DRUG-RESISTANCE ; P-GLYCOPROTEIN ; SILVER NANOPARTICLES ; GENE DELIVERY ; BREAST-CANCER ; ALPHA-TUBULIN ; PRODRUG-LIKE ; HELA-CELLS
资助项目National Basic Research Program of China (973 Program)[2014CB931900] ; National Basic Research Program of China (973 Program)[2013CB932503] ; NSFC, China[81373357] ; NSFC, China[81422048] ; NSFC, China[81673382] ; NSFC, China[81521005]
WOS研究方向Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000408178400004
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/272528]  
专题药物制剂研究中心
通讯作者Xu, Qin; Wang, Jianxin; Huang, Yongzhuo
作者单位1.Guangzhou Univ Chinese Med, 12 Ji Chang Rd, Guangzhou 510450, Guangdong, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Medica, 501 Haike Rd, Shanghai 201203, Peoples R China;
3.Fudan Univ, Sch Pharm, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
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Tang, Yisi,Liang, Jianming,Wu, Aihua,et al. Co-Delivery of Trichosanthin and Albendazole by Nano-Self Assembly for Overcoming Tumor Multidrug-Resistance and Metastasis[J]. ACS APPLIED MATERIALS & INTERFACES,2017,9(32):26648-26664.
APA Tang, Yisi.,Liang, Jianming.,Wu, Aihua.,Chen, Yingzhi.,Zhao, Pengfei.,...&Huang, Yongzhuo.(2017).Co-Delivery of Trichosanthin and Albendazole by Nano-Self Assembly for Overcoming Tumor Multidrug-Resistance and Metastasis.ACS APPLIED MATERIALS & INTERFACES,9(32),26648-26664.
MLA Tang, Yisi,et al."Co-Delivery of Trichosanthin and Albendazole by Nano-Self Assembly for Overcoming Tumor Multidrug-Resistance and Metastasis".ACS APPLIED MATERIALS & INTERFACES 9.32(2017):26648-26664.

入库方式: OAI收割

来源:上海药物研究所

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