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Synthesis and characterization of cisplatin‐loaded, EGFR‐targeted biopolymer and in vitro evaluation for targeted delivery
Author(s) -
Geng Xu,
Ye Haifeng,
Feng Zhen,
Lao Xun,
Zhang Li,
Huang Jing,
Wu ZiRong
Publication year - 2012
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34207
Subject(s) - biopolymer , cisplatin , drug delivery , materials science , in vitro , cytotoxicity , flow cytometry , targeted drug delivery , cancer research , epidermal growth factor receptor , targeted therapy , pharmacology , nanotechnology , chemotherapy , cancer , chemistry , medicine , microbiology and biotechnology , receptor , biochemistry , biology , composite material , polymer
The design of smart targeted drug delivery systems that deliver drugs to specific cancer cells will give rise to cancer treatments with better efficacy and lower toxicity levels. We report the development and characterizations of maleimide‐functionalized biopolymer (Mal‐PGA‐Asp) as an effective targeted drug delivery carrier synthesized from an amidation reaction between aspartylated PGA (PGA‐Asp) and N ‐(maleimidohexanoyl)‐ethylenediamine (NME). The epidermal growth factor receptor (EGFR) targeting peptide (TP13) was conjugated to Mal‐PGA‐Asp to obtain the targeting carrier (TP13‐Mal‐PGA‐Asp). Cisplatin was finally loaded by complexation to form a biocompatible and tumor targeted therapeutic drug (TP13‐Mal‐PGA‐Asp3‐Pt). The resultant biopolymer with an average size 87 ± 28 nm showed a sustainable release profile with a half‐maximal release time ( t 1/2 ) of approximately 15 h in physiological saline. Fluorescence imaging and flow cytometry analysis revealed that TP13 significantly enhanced the cellular uptake of TP13‐Mal‐PGA‐Asp3‐Pt in the human hepatoma cell line SMMC‐7721. The IC 50 value demonstrated the superior anticancer activity of TP13‐Mal‐PGA‐Asp3‐Pt over PGA‐Asp‐Pt. Therefore, the newly developed drug carrier (TP13‐Mal‐PGA‐Asp) obtained in this study may provide an efficient and targeted delivery of anticancer drugs, presenting a promising targeted chemotherapy in EGFR‐positive cancers. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2839–2848, 2012.