Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin- cisplatin nanoparticles

Xiang Hong Peng; Yiqing Wang; Donghai Huang; Yuxiang Wang; Hyung Juc Shin; Zhengjia Chen; Michael B. Spewak; Hui Mao; Xu Wang; Ying Wang; Zhuo Chen; Shuming Nie; Dong M. Shin

doi:10.1021/nn202410f

Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin- cisplatin nanoparticles

Xiang Hong Peng, Yiqing Wang, Donghai Huang, Yuxiang Wang, Hyung Juc Shin, Zhengjia Chen, Michael B. Spewak, Hui Mao, Xu Wang, Ying Wang, Zhuo Chen, Shuming Nie, Dong M. Shin

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	9480-9493
Number of pages	14
Journal	ACS Nano
Volume	5
Issue number	12
DOIs	https://doi.org/10.1021/nn202410f
State	Published - Dec 27 2011
Externally published	Yes

Keywords

EGFR
cisplatin
drug delivery
heparin
lung cancer
nanoparticles
tumor targeting

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

Online availability

10.1021/nn202410f

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title = "Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin- cisplatin nanoparticles",

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.",

keywords = "EGFR, cisplatin, drug delivery, heparin, lung cancer, nanoparticles, tumor targeting",

author = "Peng, {Xiang Hong} and Yiqing Wang and Donghai Huang and Yuxiang Wang and Shin, {Hyung Juc} and Zhengjia Chen and Spewak, {Michael B.} and Hui Mao and Xu Wang and Ying Wang and Zhuo Chen and Shuming Nie and Shin, {Dong M.}",

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TY - JOUR

T1 - Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin- cisplatin nanoparticles

AU - Peng, Xiang Hong

AU - Wang, Yiqing

AU - Huang, Donghai

AU - Wang, Yuxiang

AU - Shin, Hyung Juc

AU - Chen, Zhengjia

AU - Spewak, Michael B.

AU - Mao, Hui

AU - Wang, Xu

AU - Wang, Ying

AU - Chen, Zhuo

AU - Nie, Shuming

AU - Shin, Dong M.

PY - 2011/12/27

Y1 - 2011/12/27

N2 - 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.

AB - 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.

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KW - cisplatin

KW - drug delivery

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KW - lung cancer

KW - nanoparticles

KW - tumor targeting

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Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin- cisplatin nanoparticles

Abstract

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