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Drug delivery systems must overcome a series of biological barriers to escort therapeutical agents to specific pathological site. These include both extracellular barriers and intracellular barriers. To overcome extracellular barriers, the vehicles should have high stability and prolonged circulation time in the blood stream, and sufficient accumulation in disease site. Intracellular barriers are the subsequent barrier that determines successful drug or gene delivery, including effective cellular internalization, endosomal escape, and controllable release. Comprehensive consideration of both extracellular and intracellular barriers to targeted drug and gene delivery is critically important. Nanoparticles (NPs) based drug and gene delivery systems exhibit potential ability to overcome the biological barriers, due to their structures can be tailored to address those barriers such as release the therapeutic agents in the desired site. In this review, we will focus on recent exciting advances in designing redox sensitive nanoparticles for intracellular drug delivery. Those redox sensitive NPs are particularly concentrated on recent emerging NPs with disulfide bond linked sheddable shell like PEG.
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