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Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide
Li, Shao-Lu1,2; Wang, Yaoyi2; Zhang, Jingfang2; Wei, Wei3; Lu, Hua2

We describe here a novel targeting polyion complex (Tg-PIC) system for the delivery and intracellular release of cisplatin. Briefly, a guanidinium-pendant Pt(IV)-backboned poly-prodrug termed P(DSP-Gu) is prepared with excellent aqueous solubility, high drug-loading and high potency. To enable prolonged circulation and selective cellular internalization, P(DSP-Gu) is complexed with anisamide-end-capped poly(ethylene glycol)-block-poly(L-phosphotyrosine)-block-poly(L-leucine) (AA-PEG-PpY-PLeu) to yield Tg-PIC via electrostatic coacervation. Tg-PIC is stabilized by hydrogen bonding between phosphate and guanidinium, the PEG corona, and the helical poly(L-leucine) segment forming the hydrophobic core. The anisamide group, a high affinity ligand recognizing the sigma (sigma) receptors that are overexpressed on many human malignancies including prostate cancer, is incorporated at the surface of the Tg-PIC for active targeting and efficient internalization. In vitro, the Tg-PICs show targeted and efficient internalization into sigma receptor-positive PC3 cells, and can release toxic Pt(II) species due to the degradation of P(DSP-Gu) under the intracellular reducing conditions. In vivo, the Tg-PICs exhibit superior antitumor efficacy with reduced toxicity. Thus, the system holds considerable promise towards more effective and safe nanomedicine.

WOS HeadingsScience & Technology ; Technology
Indexed BySCI
WOS KeywordRing-opening Polymerization ; Drug-delivery ; Co-delivery ; Prostate-cancer ; Sirna Delivery ; Responsive Polymers ; Anticancer Activity ; Block-copolymers ; In-vitro ; Therapy
WOS Research AreaMaterials Science
WOS SubjectMaterials Science, bioMaterials
Funding OrganizationNational Key Research and Development Program of China(2016YFA0201400) ; State High-Tech Development Program of China (863 Program)(2015AA020941) ; National Natural Science Foundation of China(NSFC21434008) ; State Key Laboratory of Biochemical Engineering(2015KF-01) ; China Postdoctoral Science Foundation(2016M600847) ; Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences
WOS IDWOS:000418072200012
Citation statistics
Document Type期刊论文
Corresponding AuthorLu, Hua
Affiliation1.Tianjin Polytech Univ, Sch Mat Sci & Engn, State Key Lab Separat Membranes & Membrane Proc, Tianjin 300387, Peoples R China
2.Peking Univ, Key Lab Polymer Chem & Phys, Beijing Natl Lab Mol Sci,Minist Educ, Ctr Soft Matter Sci & Engn,Coll Chem & Mol Engn, Beijing 100871, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 10090, Peoples R China
Recommended Citation
GB/T 7714
Li, Shao-Lu,Wang, Yaoyi,Zhang, Jingfang,et al. Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide[J]. JOURNAL OF MATERIALS CHEMISTRY B,2017,5(48):9546-9557.
APA Li, Shao-Lu,Wang, Yaoyi,Zhang, Jingfang,Wei, Wei,&Lu, Hua.(2017).Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide.JOURNAL OF MATERIALS CHEMISTRY B,5(48),9546-9557.
MLA Li, Shao-Lu,et al."Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide".JOURNAL OF MATERIALS CHEMISTRY B 5.48(2017):9546-9557.
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