Phosphatase-triggered cell-selective release of a Pt(iv)-backboned prodrug-like polymer for an improved therapeutic index.
We describe here the synthesis and cell-selective delivery of a cationic Pt(iv)-backboned prodrug-like polymer P(DSP-DAEP). P(DSP-DAEP) features excellent aqueous solubility, unusually high (44.5%) drug loading, can be rapidly reduced to release the active cisplatin, and is more potent than its small molecular Pt(iv) precursor DSP. P(DSP-DAEP) can be formulated with an oppositely charged methoxyl poly(ethylene glycol)-block-poly(l-phosphotyrosine) (mPEG-b-PpY) to afford a polyion micelle (Pt-PIC) by taking advantage of polyelectrolyte coacervation. Preliminary in vitro cellular uptake and cytotoxicity assays indicate that Pt-PIC exhibits receptor (surface alkaline phosphatase)-dependent uptake and cytotoxicity. Overall, our results suggest a new approach to the improved therapeutic index of platinum-based anticancer drugs via cell-selective delivery.
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. chemhualu@pku.edu.cn.
Shao-Lu
SL
Li
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. chemhualu@pku.edu.cn.
Yingqin
Y
Hou
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. chemhualu@pku.edu.cn.
Yali
Y
Hu
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. chemhualu@pku.edu.cn.
Jin
J
Yu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 10090, People's Republic of China. weiwei@ipe.ac.cn.
Wei
W
Wei
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. chemhualu@pku.edu.cn.
Hua
http://orcid.org/0000-0003-2180-3091
H
Lu
D045744:Cell Line, Tumor; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010984:Platinum / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D000076162:Therapeutic Index; D014867:Water / Q000737:chemistry
D011108:Polymers; D011355:Prodrugs; D014867:Water; D010984:Platinum; D010744:Phosphoric Monoester Hydrolases