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Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery
Hou, Yingqin1; Wang, Yaoyi1; Wang, Ruijue3; Bao, Weier2; Xi, Xiaobo2; Sun, Yunlong1; Yang, Shengtao3; Wei, Wei2; Lu, Hua1

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.

KeywordPoly(Phosphotyrosine) Cisplatin Atp-responsive Drug Delivery Irgd
WOS HeadingsScience & Technology ; Technology
Indexed BySCI
WOS KeywordAnticancer 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
WOS Research AreaScience & Technology - Other Topics ; Materials Science
WOS SubjectNanoscience & Nanotechnology ; Materials Science, Multidisciplinary
Funding OrganizationNational Key Research and Development Program of China(2016YFA0201400) ; National Natural Science Foundation of China(21434008 ; Open Funding Project of the State Key Laboratory of Biochemical Engineering(2015KF-01) ; Beijing Talents Fund(2015000021223ZK20) ; 21622608)
WOS IDWOS:000402691600011
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Document Type期刊论文
Affiliation1.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
Recommended Citation
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.
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