Supramolecular Microspheres Fabricated from Macrocycle-Incorporated Polymers and Their Biomedical Applications Based on Host-Guest Recognition

Microspheres have emerged as a pivotal platform for micron-scale drug delivery, yet their utility has been greatly hindered by limitations in biodegradability, drug loading efficiency, and release kinetics, underscoring the urgent need for a next-generation microsphere platform that integrates high performance, scalability, and multifunctionality. Leveraging host–guest recognition, a series of macrocycle-incorporated polymers is synthesized and engineered a new class of supramolecular microspheres, which feature precisely tunable components, including host molecules, guest cargoes, and polymer components, as well as customizable morphologies, while enabling cost-effective, large-scale production. Following systematic validation of the host–guest recognition between β-cyclodextrin (β-CD) and lanreotide, we developed supramolecular microspheres (LAN@S-CPMs) that achieve a drug loading capacity and release duration approximately twice that of conventional microspheres, effectively curbing the disease progression of acromegaly. Beyond sustained release, porous supramolecular microspheres (S-P[5]PMs-p) fabricated from the pillar[5]arene (P[5])-incorporated polymer exhibit exceptional efficiency in spermine adsorption, while mineralized supramolecular microspheres (SORA@S-CPMs-p@CaCO₃) loaded with sorafeinib (SORA) are successfully employed in embolization therapy, achieving more complete vascular occlusion compared to non-mineralized microspheres. The modular design of supramolecular microspheres and facile scalability in production offer a transformative platform to overcome the multifaceted challenges currently faced by microsphere-based delivery systems.