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Int. J. Mol. Sci. 2015, 16(7), 16263-16274; doi:10.3390/ijms160716263

RGD Peptides-Conjugated Pluronic Triblock Copolymers Encapsulated with AP-2α Expression Plasmid for Targeting Gastric Cancer Therapy in Vitro and in Vivo

1,2,†,* , 1,2,†
,
2
,
1,2
,
3
,
4
,
5
and
5,*
1
Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China
2
Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
3
Department of Anesthesiology, the First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China
4
Department of Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
5
Department of Orthopedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Antonella Piozzi
Received: 12 May 2015 / Revised: 29 June 2015 / Accepted: 30 June 2015 / Published: 17 July 2015
(This article belongs to the Section Biomaterial Sciences)
View Full-Text   |   Download PDF [1672 KB, uploaded 17 July 2015]   |  

Abstract

Gastric cancer, a high-risk malignancy, is a genetic disease developing from a cooperation of multiple gene mutations and a multistep process. Gene therapy is a novel treatment method for treating gastric cancer. Here, we developed a novel Arg-Gly-Asp (RGD) peptides conjugated copolymers nanoparticles-based gene delivery system in order to actively targeting inhibit the growth of gastric cancer cells. These transcription factor (AP-2α) expression plasmids were also encapsulated into pluronic triblock copolymers nanoparticles which was constituted of poly(ethylene glycol)-block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO-block-PPO-block-PEO, P123). The size, morphology and composition of prepared nanocomposites were further characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) analysis, these nanocomposites have minor effects on the proliferation of GES-1 cells but significantly decreased the viability of MGC-803, suggesting they own low cytotoxicity but good antitumor activity. The following in vivo evaluation experiments confirmed that these nanocomposites could prevent the growth of gastric cancer cells in the tumor xenograft mice model. In conclusion, these unique RGD peptides conjugated P123 encapsulated AP-2α nanocomposites could selectively and continually kill gastric cancer cells by over-expression of AP-2α in vitro and in vivo; this exhibits huge promising applications in clinical gastric cancer therapy. View Full-Text
Keywords: gastric cancer; gene therapy; triblock copolymers; AP-2α; RGD gastric cancer; gene therapy; triblock copolymers; AP-2α; RGD
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, W.; Liu, Z.; Sun, P.; Fang, C.; Fang, H.; Wang, Y.; Ji, J.; Chen, J. RGD Peptides-Conjugated Pluronic Triblock Copolymers Encapsulated with AP-2α Expression Plasmid for Targeting Gastric Cancer Therapy in Vitro and in Vivo. Int. J. Mol. Sci. 2015, 16, 16263-16274.

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