Target-Induced Nanoparticle Assemblies: A Comprehensive Review on Strategies for Nucleic Acid Functionalization, Biosensing, and Drug Delivery Applications

Fundamental studies on nanoparticle superstructures or core-satellite assemblies and their interactions with biomolecules have led to advancements in nanobiotechnology. Consequently, some novel nucleic acid (NA) biosensing, diagnostics, and imaging approaches have been developed by functionalizing the surface of nanoparticles with target-specific analytes. For functionalization, multivalent nanoparticles are chosen over monovalent ones because they can enhance the concentration of probes on the nanoparticle surface and simultaneously bind to multiple target sites, leading to specific and sensitive detection, primarily in the case of target NAs with low-abundance target. Selection of appropriate satellite (shell) and core nanoparticles is crucial for building assemblies that can improve the resistance of DNA against serum degradation and nuclease activity by several folds compared with those of un-assembled particles. Structural modification of NPs via covalent ligation with DNA or miRNA using synthetic click chemistry approaches resulted in the formation of dimers/tetramers, which could ease the delivery of DNA-intercalating drugs and simultaneously sense target biomarkers in the cellular environment, showing the synergistic applications of multivalent assemblies. This review provides an overview of the design strategies and chemistries involved in the loading of nucleic acid probes onto the NP surface, synthesis of PEG ligands, and purification and characterization techniques for assemblies (dimer, trimer, and multimer). In addition, the applications of NP assemblies in biosensing miRNA, strategies and challenges involved in the intracellular detection of miRNA, colorimetric, SERS, and electrochemical techniques for bacterial/virus detection, and drug delivery applications are discussed. Finally, the advantages, challenges, and future perspectives in commercializing this technology are comprehensively elucidated.