Design of Chemically Programmable Nanomaterials for Organ-Selective Targeting.

Achieving precise and predictable organ-selective delivery remains a central challenge in nanomedicine, as the in vivo fate of nanoparticles is governed by complex biological interactions. Chemical composition has emerged as a powerful and programmable design dimension to address this challenge, enabling rational modulation of nanomaterial-biological interactions and organ tropism. In this perspective, we frame nanomaterial engineering as a chemically programmable design paradigm, highlighting how constituent design and surface functionalization jointly determine targeting and therapeutic performance. We systematically survey recent advances in organ-selective delivery across major targets and discuss the mechanistic principles underlying compositional programmability. We further highlight emerging analytical tools and outline future opportunities in stimuli-responsive design, multifunctional targeting, and machine learning-assisted nanomaterial development. Collectively, this perspective establishes chemical composition as a universal programmable parameter for precision nanomedicine and offers guiding principles for the rational design of next-generation organ-selective therapeutics.