Tumor microenvironment-induced structure changing drug/gene delivery system for overcoming delivery-associated challenges.

Abstract Nano-drug/gene delivery systems (DDS) are powerful weapons for the targeted delivery of various therapeutic molecules in treatment of tumors. Nano systems are being extensively investigated for drug and gene delivery applications because of their exceptional ability to protect the payload from degradation in vivo, prolong circulation of the nanoparticles (NPs), realize controlled release of the contents, reduce side effects, and enhance targeted delivery among others. However, the specific properties required for a DDS vary at different phase of the complex delivery process, and these requirements are often conflicting, including the surface charge, particle size, and stability of DDS, which severely reduces the efficiency of the drug/gene delivery. Therefore, researchers have attempted to fabricate structure, size, or charge changeable DDS by introducing various tumor microenvironment (TME) stimuli-responsive elements into the DDS to meet the varying requirements at different phases of the delivery process, thus improving drug/gene delivery efficiency. This paper summarizes the most recent developments in TME stimuli-responsive DDS and addresses the aforementioned challenges.