Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer

doi:10.1021/acsami.7b07132

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer
	Wei, Yan 3; Wang, Yuxi 1,3; Xia, Dengning 3; Guo, Shiyan 3; Wang, Feng 2; Zhang, Xinxin3 ; Gan, Yong3
刊名	ACS APPLIED MATERIALS & INTERFACES
	2017-08-02
卷号	9 期号:30 页码:25138-25151
关键词	pancreatic cancer fibrotic matrix pancreatic stellate cells thermosensitive liposomes codelivery HSA-drug complexes PSCs-PDA interaction
ISSN号	1944-8244
DOI	10.1021/acsami.7b07132
文献子类	Article
英文摘要	Fibrotic stroma and tumor-promoting pancreatic stellate cells (PSCs), critical characters in the pancreatic ductal adenocarcinoma (PDA) microenvironment, promote a tumor-facilitating environment that simultaneously prevents drug penetration into tumor foci and stimulates tumor growth. Nab-PTX, a human serum albumin (HSA) nanoparticle of paclitaxel (PTX), indicates enhanced matrix penetration in PDA probably due to its small size in vivo and high affinity of HSA with secreted protein acidic and rich in cysteine (SPARC), overexpressed in the PDA stroma. However, this HSA nanoparticle shows poor drug blood retention because of its weak colloidal stability in vivo, thus resulting in insufficient drug accumulation within tumor. Encapsulating HSA nanoparticles into the internal aqueous phase of ordinary liposomes improves their blood retention and the following tumor accumulation, but the large 200 nm size and shielding of HSA in the interior might make it difficult for this hybrid nanomedicine to penetrate the fibrotic PDA matrix and promote bioavailability of the payload. In our current work, we prepared tun HSA complexes with an antitumor drug (PTX) and an anti-PSC drug (ellagic acid, EA), and these two HSA drug complexes were further coencapsulated into thermosensitive liposomes (TSLs). This nanomedicine was named TSL/HSA-PE. The use of TSL/HSA-PE could improve drug blood retention, and upon reaching locally heated tumors, these TSLs can rapidly release their payloads (HSA drug complexes) to facilitate their further tumor accumulation and matrix penetration. With superior tumor accumulation, impressive matrix penetration, and simultaneous action upon tumor cells and PSCs to disrupt PSCs PDA interaction, TSL/HSA-PE treatment combined with heat exhibited strong tumor growth inhibition and apoptosis in vivo.
资助项目	China Postdoctoral Science Foundation[2016M600342]
WOS关键词	HUMAN SERUM-ALBUMIN ; TUMOR-TARGETED DELIVERY ; DUCTAL ADENOCARCINOMA ; BOUND PACLITAXEL ; CONJUGATED NANOPARTICLES ; VASCULAR-PERMEABILITY ; SPARC EXPRESSION ; STELLATE CELLS ; CREMOPHOR-FREE ; IN-VITRO
WOS研究方向	Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000407089300010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272533]
专题	药物制剂研究中心
通讯作者	Gan, Yong
作者单位	1.Univ Sci & Technol China, Nano Sci & Technol Inst, 166 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China; 2.Shanghai Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Wei, Yan,Wang, Yuxi,Xia, Dengning,et al. Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer[J]. ACS APPLIED MATERIALS & INTERFACES,2017,9(30):25138-25151.
APA	Wei, Yan.,Wang, Yuxi.,Xia, Dengning.,Guo, Shiyan.,Wang, Feng.,...&Gan, Yong.(2017).Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer.ACS APPLIED MATERIALS & INTERFACES,9(30),25138-25151.
MLA	Wei, Yan,et al."Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer".ACS APPLIED MATERIALS & INTERFACES 9.30(2017):25138-25151.