Layer-by-Layer Assembled Polypeptide Capsules for Platinum-Based Pro-Drug Delivery

Platinum(IV), a pro-drug of platinum(II), was conjugated to poly(l-lysine) (PLL), and then assembled with poly(glutamic acid) (PGA) through a layer-by-layer (LbL) approach on colloidal silica templates. After removal of the templates, biodegradable PGA/PLL-Pt(IV) multilayer capsules (diameter = 0.5...

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Bibliographic Details
Published in:Bioconjugate chemistry 2012-12, Vol.23 (12), p.2335-2343
Main Authors: Zhou, Dongfang, Xiao, Haihua, Meng, Fanbo, Zhou, Shaoyang, Guo, Jinshan, Li, Xiaoyuan, Jing, Xiabin, Huang, Yubin
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cancer
Cell Line, Tumor
Cell Survival - drug effects
Cells
Cisplatin - administration & dosage
Cisplatin - chemistry
Cisplatin - pharmacology
Colloids
Coordination Complexes - chemical synthesis
Coordination Complexes - pharmacology
Cytotoxicity
Drug Carriers - chemical synthesis
Endocytosis
Humans
Hydrogen-Ion Concentration
Kinetics
Microscopy, Confocal
Platinum
Polyglutamic Acid - chemistry
Polylysine - chemistry
Prodrugs - chemistry
Prodrugs - pharmacology
Prodrugs - toxicity
Scanning electron microscopy
Silicon Dioxide - chemistry
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Summary:Platinum(IV), a pro-drug of platinum(II), was conjugated to poly(l-lysine) (PLL), and then assembled with poly(glutamic acid) (PGA) through a layer-by-layer (LbL) approach on colloidal silica templates. After removal of the templates, biodegradable PGA/PLL-Pt(IV) multilayer capsules (diameter = 0.5 μm) with 10 μg of platinum incorporated into each bilayer were obtained. Under acidic and/or reductive conditions, the amount and rate of platinum released from the capsules were increased, which are desirable traits for platinum-based anticancer drug delivery systems. Furthermore, in vitro evaluation showed that the PGA/PLL-Pt(IV) multilayer microcapsules displayed higher cytotoxicity (IC50Pt = 3.5 μg/mL) against colon cancer cells CT-26 than that of free cisplatin (IC50Pt = 8.6 μg/mL). This enhanced cytotoxicity was attributed to the effective internalization of the capsules by the cancer cells, which was observed by confocal laser scanning microscopy (CLSM) imaging.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc300144e