Programmable nanomedicine via bioorthogonal molecular engineering

Bioorthogonal chemistry provides a versatile strategy for programming nanomedicines beyond static carrier design. It enables post-synthetic installation of functional modules on nanoparticle surfaces, spatiotemporal control of payload activation and release, and higher-order functions arising from nanoparticle aggregation or nanoparticle-cell conjugation in diseased tissues. These capabilities allow nanomedicines to be activated more selectively in space and time and to generate functions that are difficult to achieve with conventional formulations. This review summarizes recent advances in multiscale bioorthogonal engineering for programmable nanomedicines, focusing on surface functionalization, molecular control of drug release, and interparticle or cell-associated assembly, and discusses challenges and future directions.