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Self-synergistic pH-sensitive Poly (β-amino ester) Nanoparticles Co-deliver Doxorubicin and RNA for Reversal of Multidrug Resistance of Breast Cancer
Update time: 2014-07-24
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Multidrug resistance (MDR) is one of the main obstacles to the successful chemotherapy of breast cancer because MDR could result in increase of drug efflux, activation of the detoxification system, DNA repair and blockage of apoptosis, etc.

The research group led by Prof. LIYaping in Shanghai Institute of MateriaMedica, Chinese Academy of Sciences provided an efficacious tool to the treatment of MDR of breast cancer by an appropriate co-delivery system for chemotherapeutic agents and nucleic acid drugs.

In this work, a new amphiphilic poly(β-amino ester), poly[(1,4-butanediol)-diacrylate-β-5-polyethylenimine]-block-poly[(1,4-butanediol)-diacrylate-β-5-hydroxyamylamine] (PDP-PDHA) was synthesized, and the doxorubicin (DOX) and survivin, an apoptosis inhibiting protein, -targeting shRNA (shSur) co-loading nanoparticle (PDNs) based on it was prepared.

Further studies demonstrated that the application of the pH-sensitive poly[(1,4-butanediol) diacrylate-β-5-hydroxy amylamine] (PDHA) block in chemical drug delivery endowed PDNs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the cytotoxicity of DOX and the transfection efficiency.

PDNs also increased the DOX accumulation, down-regulated the survivin expression, induced cell apoptosis and changed the cell cycle in MCF-7/ADR cells. In the MCF-7/ADR tumor-bearing mice models, PDNs raised the accumulation of both DOX and shSur in the tumor tissue after administrated intravenously, resulting in almost complete inhibiton of the tumor growth.

This research work which performed by graduate student TANG Shan and guided by Prof. LI Yapingprovides a new idea to therapy the drug resistant breast cancer and has been recently published in “Biomaterials”(IF=7.604).

Full Texthttp://www.sciencedirect.com/science/article/pii/S0142961214003998 

 

 
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