Cross-Linked Small-Molecule Micelle-Based Drug Delivery System: Concept, Synthesis, and Biological Evaluation

Lessons from the covalent capture of small-molecule self-assemblies (monomer molecular weight of <500.0) are applied to grow a generic cross-linked small-molecule micelle-based drug delivery system (CSM-DDS), which has significant advantages over the popular polymeric micelle-based drug delivery systems in terms of drug loading, stability, monomer purity, and cost of preparation. A proof-of-concept CSM-DDS constructed by one-step synthesized amphiphile 1 with anticancer drug gemcitabine confirms the feasibility of the new strategy via its high drug loading content (up to 58%), robust stability, superior predictable biosafety, facile functionalization, and remarkable anticancer activity both in vitro and in vivo.