Surface-functionalized nanostructures are at the forefront of biotechnology, providing new opportunities for biosensors, drug delivery, therapy, and bioimaging applications. The modification of nanostructures significantly impacts the performance and success of various applications by enabling selective and precise targeting. This review elucidates widely practiced surface modification strategies, including click chemistry, cross-coupling, silanization, aldehyde linkers, active ester chemistry, maleimide chemistry, epoxy linkers, and other protein and DNA-based methodologies. We also delve into the application-focused landscape of the nano-bio interface, emphasizing four key domains: therapeutics, biosensing, environmental monitoring, and point-of-care technologies, by highlighting prominent studies. The insights presented herein pave the way for further innovations at the intersection of nanotechnology and biotechnology, providing a useful handbook for beginners and professionals. The review draws on various sources, including the latest research articles (2018-2023), to provide a comprehensive overview of the field.
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