Bioorthogonal reaction mediated size transformation clustered nanosystems for potentiating bioimaging and drug delivery

Abstract

Continuous advances have been witnessed in the booming of size variable nanosystems for molecular imaging and therapy. These nanosystems usually exhibit in situ size transformation, which promotes optimized biodisrution, retention and peneratrion in lesions. Bioorthogonal reactions has been introduced as a useful tool to develop size variable nanosystems. In general, researchers modify controllable blocks (including pH adjustment, disulfide reduction, and/or enzymatic hydrolysis) masked bioorthogonal handles on the nanoparticles or small molecules to develop biocompatible size variable nanosystems. These nanosystems undergo precise click cycloaddition and self-assemble to nanoaggregate in situ, showing enhanced tissue accumulation and retention. These advantages have demonstrated great promise to improve imaging quality and therapeutic outcomes with high effectiveness and controllability. Up to date, this strategy has been widely introduced to construct bioimaging probes or nanomedicines. To gain a comprehensive understanding of the strategy, in this review, we focus on bioorthogonal reaction mediated size variable nanosystems reported in recent five years, present their application for bioimaging and therapy, and elucidate the mechanism of bioorthogonal reactions. Based on these efforts, challenges and future research directions in this area are also discussed in the end.