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Bio-functionalized nanoparticles for overcoming multidrug resistance in cancer
Update time: 2014-07-22
Author: 甘勇组-张馨欣
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Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapyand interest isgrowing in the development of drug delivery systems using nanotechnology to reverse MDR in cancer. Drug delivery system based on nanoparticles can bypass the efflux pump transportand accumulate in cells by passive or active targeting. However, intrinsic instability of liposomes and other lipid-encapsulated nanoplatforms make them vulnerable to unexpected leakage orpremature drug release in vivo before reaching the target site,thereby causing systemic toxicity and inevitably exposethe MDR transporter.

Researchers from Dr. GAN Yong’s group, Shanghai Institute of Materia Medica, designed a polymer-lipid combined layer coatedMSNs (PLS-MSNs) to enhance the antitumor efficacy against MDRcancer cells.Functional polymer-lipid coating material, P123-DOPE, was synthesized by combining the drug efflux transporter inhibitor Pluronic block copolymers with pH sensitivephospholipid DOPE.

By coating MSNs with P123-DOPE, the nanocarrier PLS-MSNs are expected to retainand protect guest molecules before reaching the target cells, and the coated layer can readily disrupt to release antitumor drugs after uptake by cells, thus minimizing toxicity and maximizing effectiveness of drugs. Moreover, functional material P123-DOPE in thecoated layer can act as a “door blocker” and prevent drugs from being pumped out of MDR cancer cells.Compared to free CPT-11, PLS-MSNs resulted in a maximum increase in the intracellular CPT-11 concentration (12.9-fold), had 7.1-fold higher cytotoxicity and processed a stronger cell cycle arrest in MCF-7/BCRP cells.

This study was published on Biomaterials (Xinxin Zhang,Feifei Li, et at, 2014,35: 3650-3665) on 24 January,2014 and was supported by the National Natural ScienceFoundation of China (grant number 30901865), Natural ScienceFoundation of Hebei Province of China (grant number C2011319010)and National Key Technology Research and Development Programof China during the “12th Five-Year Plan” (grant number2012ZX09301001-001).

Full text:http://dx.doi.org/10.1016/j.biomaterials.2014.01.013


Figure1. The intracellular pathways and release profiles of PLS-MSNs.





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