Programmable next-generation supramolecular self-assembled materials as drug delivery systems

Supramolecular self-assembly, driven by noncovalent interactions, serves as a fundamental principle for constructing complex functional systems (biological membranes, proteins, and DNA). Inspired by these natural paradigms, biomimetic self-assembly strategies have promoted the development of drug delivery systems (DDSs), including liposomes, lipid nanoparticles (LNPs), and virus-like particles. While these nanomedicines are clinically established, they continue to face persistent challenges, including maintaining drug stability and activity, achieving targeted delivery, overcoming biological barriers, and ensuring efficient intracellular release. Overcoming these obstacles requires the rational design of next-generation drug delivery materials. In this review, a comprehensive analysis of supramolecular self-assembled materials (SAMs) is provided. It traces the development and self-assembly mechanisms of SAMs. It defines the characteristics of next-generation SAMs, centered on their programmability, and focuses on introducing the innovative design strategy guidelines for next-generation SAMs. These guidelines fully embody the high programmability, precise size/morphology control capabilities, and multifunctional properties of SAMs. Furthermore, it discusses the latest application progress of SAMs in treating various diseases, and emphasizes the future strategies and challenges of SAM-based DDSs, aiming to facilitate broader clinical applications and benefit human health.