| Literature DB >> 22032622 |
Xiang-Hong Peng1, Yiqing Wang, Donghai Huang, Yuxiang Wang, Hyung Juc Shin, Zhengjia Chen, Michael B Spewak, Hui Mao, Xu Wang, Ying Wang, Zhuo Georgia Chen, Shuming Nie, Dong M Shin.
Abstract
The clinical application of cis-diamminedichloroplatinum(II) (DDP, cisplatin) for cancer therapy is limited by its nonspecific biodistribution and severe side effects. Here, we have developed EGFR-targeted heparin-DDP (EHDDP) nanoparticles for tumor-targeted delivery of DDP. This nanoparticle delivery system possesses the following unique properties: (i) succinic anhydride-modified heparin is biocompatible and biodegradable with no anticoagulant activity; (ii) single-chain variable fragment anti-EGFR antibody (ScFvEGFR) was conjugated to the nanoparticles as an EGFR-targeting ligand. Our results showed that EHDDP nanoparticles can significantly increase the intracellular concentrations of DDP and Pt-DNA adducts in EGFR-expressing non-small cell lung cancer H292 cells via an EGFR-mediated pathway. Compared to the free DDP, significantly prolonged blood circulation time and improved pharmacokinetics and biodistribution of Pt were observed after systemic delivery of the EHDDP nanoparticles. The new EHDDP nanoparticle delivery system significantly enhanced antitumor activity of DDP without weight loss or damage to the kidney and spleen in nude mice bearing H292 cell tumors.Entities:
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Year: 2011 PMID： 22032622 PMCID： PMC3275811 DOI： 10.1021/nn202410f
Source DB: PubMed Journal: ACS Nano ISSN： 1936-0851 Impact factor: 15.881