Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Deliver
† Beijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People’s Republic of China
‡ State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 10090, People’s Republic of China
§ College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu 610041, People’s Republic of China
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 complexation. 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 a R9-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-platinum complexation can be exploited for effective delivery of CDDP, and suggests a paradigm shift of constructing nanosystems for other anticancer metallodrugs.
相關(guān)產(chǎn)品
免責(zé)聲明
- 凡本網(wǎng)注明“來源:化工儀器網(wǎng)”的所有作品,均為浙江興旺寶明通網(wǎng)絡(luò)有限公司-化工儀器網(wǎng)合法擁有版權(quán)或有權(quán)使用的作品,未經(jīng)本網(wǎng)授權(quán)不得轉(zhuǎn)載、摘編或利用其它方式使用上述作品。已經(jīng)本網(wǎng)授權(quán)使用作品的,應(yīng)在授權(quán)范圍內(nèi)使用,并注明“來源:化工儀器網(wǎng)”。違反上述聲明者,本網(wǎng)將追究其相關(guān)法律責(zé)任。
- 本網(wǎng)轉(zhuǎn)載并注明自其他來源(非化工儀器網(wǎng))的作品,目的在于傳遞更多信息,并不代表本網(wǎng)贊同其觀點(diǎn)和對其真實(shí)性負(fù)責(zé),不承擔(dān)此類作品侵權(quán)行為的直接責(zé)任及連帶責(zé)任。其他媒體、網(wǎng)站或個人從本網(wǎng)轉(zhuǎn)載時,必須保留本網(wǎng)注明的作品第一來源,并自負(fù)版權(quán)等法律責(zé)任。
- 如涉及作品內(nèi)容、版權(quán)等問題,請?jiān)谧髌钒l(fā)表之日起一周內(nèi)與本網(wǎng)聯(lián)系,否則視為放棄相關(guān)權(quán)利。