Design and development of polymeric micelles with cleavable links for intracellular drug delivery

Abstract Driven by the urgent need in practical applications of stimuli-responsive nano-carriers for intracellular drug delivery, the design and development of advanced polymeric micelles capable of responding to the intracellular environment (e.g., ions, proteins, enzymes, and pH changes) has represented a promising strategy as well as a new task in this research field during the past decade. To this end, an effective approach has been to incorporate cleavable links into the polymer structure, either to cause a structural change of the delivery systems, or to direct conjugate drug molecules which could be released on the cleavage of the links. The current review highlights the recent advance in this field and focuses on two types of polymeric micelles that can respond to the physiological signals, i.e., intracellular pH- and reduction-sensitive micelles.