Biological Stimulus-Driven Assembly/Disassembly of Functional Nanoparticles for Targeted Delivery, Controlled Activation, and Bioelimination.

Abstract

Nanoassembly technology has emerged as a powerful tool for targeted drug delivery and provides a basis for fabricating medical theranostic nanosystems. However, it is extremely difficult to concentrate nanoparticles at tumor sites, and the poor target-to-background ratio undoubtedly obstructs the accurate diagnosis and effective therapy of cancerous tissues. Importantly, the addition of biological stimulus-responsive groups to nanoassembly systems can enable a biological stimulus-driven assembly-disassembly mutual switch or structural composition/conformation change, thereby amplifying the imaging signal and/or enhancing the therapeutic effect. This progress report provides an overview of well-designed biological stimulus-responsive nanosystems that can realize precise assembly-disassembly switches by disrupting or rebuilding the intricate balance between the entropy and enthalpy of the nanosystems in response to stimuli (pH, redox, enzymes, etc.) in tumor tissues. The discussion encompasses different biological stimulus-responsive groups, fabrication approaches, and outstanding selective "turn-on" performance for efficient tumor imaging, therapy, and bioelimination. This progress report is expected to inspire more extensive research for the development of smart "turn-on" nanomaterials with increased signal-to-noise (S/N) ratios for diagnosis and drug delivery, which may pave the way for precise nanomedicine with site-specific theranostic features and biocompatibility.