Facile construction of dual-bioresponsive biodegradable micelles with superior extracellular stability and activated intracellular drug release

Reversibly crosslinked pH-sensitive micelles based on biodegradable PEG-P(TMBPEC-co-PDSC) copolymer can be prepared by self-assembly in water followed by self-crosslinking using a catalytic amount of DTT, for efficient delivery of DOX into tumor cells, giving superior stability at low concentrations with inhibited (premature) drug release, but fast and maximal drug release during the intracellular trafficking process not only activated in the mildly acidic endosomal compartments but also in the highly reductive cytoplasm and cell nuclei.218