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

doi:10.1021/acsami.7b03686

CORC > 北京大学 > 化学与分子工程学院

	Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery
	Hou, Yingqin ; Wang, Yaoyi ; Wang, Ruijue ; Bao, Weier ; Xi, Xiaobo ; Sun, Yunlong ; Yang, Shengtao ; Wei, Wei ; Lu, Hua
刊名	ACS APPLIED MATERIALS & INTERFACES
	2017
关键词	poly(phosphotyrosine) cisplatin ATP-responsive drug delivery iRGD 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
DOI	10.1021/acsami.7b03686
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.; National Key Research and Development Program of China [2016YFA0201400]; National Natural Science Foundation of China [21434008, 21622608]; Open Funding Project of the State Key Laboratory of Biochemical Engineering [2015KF-01]; Beijing Talents Fund [2015000021223ZK20]; SCI(E); ARTICLE; 21; 17757-17768; 9
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473300]
专题	化学与分子工程学院
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.
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.
MLA	Hou, Yingqin,et al."Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery".ACS APPLIED MATERIALS & INTERFACES (2017).