Recent developments in bioconjugation: From strategies to design and clinical applications

Abstract

Bioconjugation is defined as the covalent attachment of biomolecules, such as proteins, carbohydrates, nucleic acids, or lipids, to another biomolecule or functional entity such as synthetic polymers, fluorescent probes, drugs, dyes, and targeting ligands. Bioconjugation plays a key role in modern biotechnology and medicine, enabling precise control over molecular recognition, stability, and biodistribution. This review provides a comprehensive and integrative perspective on bioconjugation, encompassing both traditional and emerging strategies while critically comparing their efficiency, stability, and clinical applicability. It evaluates the strengths and limitations of various approaches, from classical amide and thiol couplings to advanced bioorthogonal click chemistry. Furthermore, the review highlights innovative directions in optimizing bioconjugation, including linker design, enhanced stability profiles, stimuli-responsive release mechanisms, and predictive release kinetics. The work integrates recent advances into a framework that addresses key challenges, such as site-specificity, immunogenicity, and scalability and offers a practical guide for next-generation diagnostics and therapeutics.