Near-infrared AIEgens as transformers to enhance tumor treatment efficacy with controllable self-assembled redox-responsive carrier-free nanodrug

Nanosized drug delivery systems (nDDS) have been extensively exploited to achieve improved therapeutic performance of chemotherapeutic drugs in cancer treatment. Carrier-free nanodrugs have recently emerged as a promising generation of nDDS. In this work, a carrier-free theranostic nanodrug was fabricated by incorporating near-infrared (NIR) emission AIEgens (NPAPF) with redox responsive camptothecin-gemcitabine amphiphilic prodrug (CPT-ss-GEM) to form self-assembled nanoparticles (NCssG NPs). The introducing of AIEgens is designed to not only endow the nDDS with NIR imaging ability but also to act as transformers to modulate the geometry of the self-assembled nanostructures from nanowires to spherical nanoparticles. Interestingly, this unique geometric effect is further demonstrated to be very crucial to the anticancer performance of the nDDS in vitro and in vivo. The AIEgens-doped spherical nanoparticles NCssG NPs showed much higher cellular uptake efficiency and tumor penetration ability, therefor achieving much stronger anticancer efficacy than free CPT/GEM mixture and CPT-ss-GEM nanowires (CssG NWs). The theranostic features of NCssG NPs were fully utilized to evaluate the redox-triggered drug release process, in vivo biodistribution and tumor targeted accumulation of NCssG NPs. This work provides a novel strategy and some useful information for the optimization of the design of theranostic nDDS to benefit for the clinic application of nanodrugs in the future.