Cisplatin-induced formation of biocompatible and biodegradable polypeptide-based vesicles for targeted anticancer drug delivery

Shirbin, Steven J., Ladewig, Katharina, Fu, Qiang, Klimak, Molly, Zhang, Xiaqing, Duan, Wei and Qiao, Greg G. 2015, Cisplatin-induced formation of biocompatible and biodegradable polypeptide-based vesicles for targeted anticancer drug delivery, Biomacromolecules, vol. 16, no. 8, pp. 2463-2474, doi: 10.1021/acs.biomac.5b00692.

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Title Cisplatin-induced formation of biocompatible and biodegradable polypeptide-based vesicles for targeted anticancer drug delivery
Author(s) Shirbin, Steven J.
Ladewig, Katharina
Fu, Qiang
Klimak, Molly
Zhang, Xiaqing
Duan, WeiORCID iD for Duan, Wei
Qiao, Greg G.
Journal name Biomacromolecules
Volume number 16
Issue number 8
Start page 2463
End page 2474
Total pages 12
Publisher American Chemical Society
Place of publication Washington, D.C.
Publication date 2015-08-10
ISSN 1526-4602
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Organic
Polymer Science
Summary Novel cisplatin (CDDP)-loaded, polypeptide-based vesicles for the targeted delivery of cisplatin to cancer cells have been prepared. These vesicles were formed from biocompatible and biodegradable maleimide-poly(ethylene oxide)114-b-poly(L-glutamic acid)12 (Mal-PEG114-b-PLG12) block copolymers upon conjugation with the drug itself. CDDP conjugation forms a short, rigid, cross-linked, drug-loaded, hydrophobic block in the copolymer, and subsequently induces self-assembly into hollow vesicle structures with average hydrodynamic diameters (Dh) of ∼ 270 nm. CDDP conjugation is critical to the formation of the vesicles. The reactive maleimide-PEG moieties that form the corona and inner layer of the vesicles were protected via formation of a reversible Diels-Alder (DA) adduct throughout the block copolymer synthesis so as to maintain their integrity. Drug release studies demonstrated a low and sustained drug release profile in systemic conditions (pH = 7.4, [Cl(-)] = 140 mM) with a higher "burst-like" release rate being observed under late endosomal/lysosomal conditions (pH = 5.2, [Cl(-)] = 35 mM). Further, the peripheral maleimide functionalities on the vesicle corona were conjugated to thiol-functionalized folic acid (FA) (via in situ reduction of a novel bis-FA disulfide, FA-SS-FA) to form an active targeting drug delivery system. These targeting vesicles exhibited significantly higher cellular binding/uptake into and dose-dependent cytotoxicity toward cancer cells (HeLa) compared to noncancerous cells (NIH-3T3), which show high and low folic acid receptor (FR) expression, respectively. This work thus demonstrates a novel approach to polypeptide-based vesicle assembly and a promising strategy for targeted, effective CDDP anticancer drug delivery.
Language eng
DOI 10.1021/acs.biomac.5b00692
Field of Research 03 Chemical Sciences
06 Biological Sciences
09 Engineering
111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy)
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, American Chemical Society
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Document type: Journal Article
Collection: School of Medicine
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