Surface engineering of nanoparticles for precision medicine

Precise delivery of nanomedicines to target sites stands as a cornerstone in advancing precision medicine. Surface chemistry acts as a pivotal regulator in this process and can influence the efficiency and specificity of nanomedicine delivery. This review focuses on three key surface engineering strategies: PEGylation, ligand orientation/density regulation, and charge/hydrophobicity modulation. This study systematically summarizes recent progress in engineering surface chemistries to optimize pharmacokinetics and target specificity, highlighting the charge-reversal strategy, transcytosis-based active transport, and tissue-targeting surface modification. The importance of multi-strategy integration for adapting to complex biological environments is emphasized, along with the need for systematic design to enhance clinical applicability. Ultimately, high-throughput screening and machine learning-driven artificial intelligence (AI) can be used to orchestrate surface engineering for next-generation precision medicines. • This review covers key surface engineering strategies (PEGylation, ligand regulation, charge modulation) to optimize nanomedicine delivery and specificity. • It emphasizes integrating multiple strategies to adapt to complex biological environments and improve nanomedicine's clinical applicability. • The review envisions using high-throughput screening and AI to advance surface engineering, creating next-generation precision medicines.