Smart transformable nanomedicines for cancer therapy.

Abstract Despite that great progression has been made in nanoparticulate drug delivery systems (nano-DDS), multiple drug delivery dilemmas still impair the delivery efficiency of nanomedicines. Rational design of smart transformable nano-DDS based on the in vivo drug delivery process represents a promising strategy for overcoming delivery obstacle of nano-DDS. In recent years, tremendous efforts have been devoted to developing smart transformable anticancer nanomedicines. Herein, we provide a review to outline the advances in this emerging field. First, smart size-reducible nanoparticles (NPs) for deep tumor penetration are summarized, including carrier degradation-induced, protonation-triggered and photobleaching-induced size reduction. Second, emerging transformable nanostructures for various therapeutic applications are discussed, including prolonging tumor retention, reversing drug-resistance, inhibiting tumor metastasis, preventing tumor recurrence and non-pharmaceutical therapy. Third, shell-detachable nanocarriers are introduced, focusing on chemical bonds breaking-initiated, charge repulsion-mediated and exogenous stimuli-triggered shell detachment approaches. Finally, the future perspectives and challenges of transformable nanomedicines in clinical cancer therapy are highlighted.