Enhanced Targeted Delivery of Doxorubicin Based on Acid Induced Charge Reversal and Combinational Stimuli‐Responsive Nanocarrier

To elevate the efficacy and to attenuate the adverse effects remain a tough challenge in exploring anticancer drug delivery systems. A nanocarrier characteristic of acid induced charge reversal and acid/redox/magnetic combinational stimuli‐responsiveness is designed. This system exhibits weaker repulsion between the carrier and the cancer cell membrane, resulting in enhanced uptake. After nanocarriers enter the cell, the system exhibits negative‐to‐positive charge reversal in response to the low intracellular pH value. Moreover, after the uptake, the carrier will be further dissociated by glutathione in cytoplasm via the reduction of the disulfide bond, leading to the rapid release of the encapsulated DOX into the nuclei. In vitro release study expresses the sequent stimulus release profile. The antitumor activity tested in CT26 tumor‐bearing mice reveals efficient therapeutic efficacy and as low adverse effect as PBS. H&E staining and immunohistochemical analysis of tumor tissues as well as pathological test of tissue sections of vital organs confirm the high antitumor activity and low tissue toxicity. Thus, the belief that this system has a good prospect in the field of cancer clinical chemotherapy.