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By incorporating pH-labile chemical linkages that cleave selectively in response to the characteristically acidic extracellular pH of the TME and the even more acidic conditions of endosomal and lysosomal compartments following cellular internalization, or redox-sensitive bonds that rupture upon encountering the markedly elevated glutathione concentrations within cancer cell cytoplasm, or enzyme-responsive substrates that are selectively cleaved by proteases and other enzymes overexpressed within the tumor stroma, intelligent nanocarriers maintain stable drug containment throughout systemic transit and release their payload rapidly and completely only after arriving at the intended intracellular destination
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