Responsive Zwitterionic Materials for Enhanced Drug Delivery

Zwitterionic materials have traditionally been recognized as exceptional antifouling agents, imparting nanocarriers with extended circulation times in vivo. Despite much studies on antifouling ability, the responsive zwitterionic materials that change physicochemical properties stimulated by mild signals are much less explored. As is known, there are multiple biological barriers in antitumor drug delivery, including the blood circulation barrier, non-specific organ distribution, elevated tumor interstitial pressure, tumor cytomembrane barrier, and lysosomal barrier. Multiple biological barriers restrict the delivery efficiency of nanocarriers to tumors, leading to a reduced therapeutic effect and increased side effects. Therefore, it is far from satisfactory to overcome the blood circulation barrier alone for classical zwitterionic antitumor materials. To address this challenge, recently developed responsive zwitterionic materials have been engineered to overcome multiple biological barriers, thereby enabling more effective antitumor drug delivery. Furthermore, responsive zwitterionic materials could respond to signals by themselves without the need of incorporating extra stimuli-responsive groups, which maintains the simplicity of the molecular structure. In this mini-review, the recent progress of antitumor zwitterionic materials responding to pH, temperature, enzyme, or reactive oxygen species is summarized. Furthermore, prospects and challenges of responsive zwitterionic materials are provided to promote better development of this field.