Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery

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	Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery
	Hou, Yingqin 1; Wang, Yaoyi 1; Wang, Ruijue 3; Bao, Weier 2; Xi, Xiaobo 2; Sun, Yunlong 1; Yang, Shengtao 3; Wei, Wei 2; Lu, Hua 1
刊名	ACS APPLIED MATERIALS & INTERFACES
	2017-05-31
卷号	9 期号:21 页码:17757-17768
关键词	poly(phosphotyrosine) cisplatin ATP-responsive drug delivery iRGD
ISSN号	1944-8244
英文摘要	To improve the therapeutic index of cisplatin (CDDP), we present here a new paradigm of drug-induced self-assembly by harnessing phosphato-platinum cornplexation. Specifically, we show that a phosphato-platinum cross-linked micelle (PpY/Pt) can be generated by using a block copolymer methoxy-poly(ethylene glycol)block-poly(L-phosphotyrosine) (mPEG-b-PpY). Coating of PpY/Pt with aR9-iRGD peptide by simple mixing affords a targeting micelle with near neutral-charged surface (iPpY/Pt). The micelles feature in well-controlled sizes below 50 nm and high, stability under physiological conditions, and can withstand various environmental stresses. Importantly, the micelles demonstrate on-demand drug release profiles in response to pathological cues such as high ATP concentration and acidic pH. In vitro, the micelles are efficiently internalized and almost equally potent compared to CDDP. Moreover, iPpY/Pt induce greater cytotoxicity than PpY/Pt in a 3D tumor spheroid model likely due to its deeper tumor penetration. In vivo, the micelles exhibit prolonged circulation half-lives, enhanced tumor accumulation, excellent tumor growth inhibition in a xenograft HeLa model and an orthotropic mammary 4T1 model, and improved safety profiles evidenced by the reduced nephrotoxicity. Together) this work demonstrates for the first time that phosphato-platinurn complexation can be exploited for effective delivery of CDDP, and suggests a paradigm shift of constructing nanosystems for other anticancer metallodrugs.
WOS标题词	Science & Technology ; Technology
类目[WOS]	Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
研究领域[WOS]	Science & Technology - Other Topics ; Materials Science
关键词[WOS]	ANTICANCER DRUG-DELIVERY ; ENHANCE THERAPEUTIC-EFFICACY ; RING-OPENING POLYMERIZATION ; OVARIAN-CANCER CELLS ; PT(IV) PRO-DRUG ; TARGETED DELIVERY ; CO-DELIVERY ; ANTITUMOR EFFICACY ; BLADDER-CANCER ; BREAST-CANCER
收录类别	SCI
语种	英语
WOS记录号	WOS:000402691600011
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/22637]
专题	过程工程研究所_生化工程国家重点实验室
作者单位	1.Peking Univ, Beijing Natl Lab Mol Sci, Minist Educ,Coll Chem & Mol Engn, Ctr Soft Matter Sci & Engn,Key Lab Polymer Chem &, Beijing 100871, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 10090, Peoples R China 3.Southwest Univ Nationalities, Coll Chem & Environm Protect Engn, Chengdu 610041, Peoples R China
推荐引用方式 GB/T 7714	Hou, Yingqin,Wang, Yaoyi,Wang, Ruijue,et al. Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery[J]. ACS APPLIED MATERIALS & INTERFACES,2017,9(21):17757-17768.
APA	Hou, Yingqin.,Wang, Yaoyi.,Wang, Ruijue.,Bao, Weier.,Xi, Xiaobo.,...&Lu, Hua.(2017).Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery.ACS APPLIED MATERIALS & INTERFACES,9(21),17757-17768.
MLA	Hou, Yingqin,et al."Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery".ACS APPLIED MATERIALS & INTERFACES 9.21(2017):17757-17768.