One Stone Several Birds: Self-Localizing Submicrocages With Dual Loading Points for Multifunctional Drug Delivery

As the core index, how to improve bioavailability of loaded cargoes is a hot topic of drug carriers. In this study, aminated β-cyclodextrin (β-CD) as a cross-linking points is first integrated into 3D poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)) network to build up a unique submicrocage (466.2 ± 47.6 nm), featuring upper critical solution temperature (UCST; ≈40 °C), high volume expansion coefficient, and excellent biocompatibility. Hereinto, hydrophobic β-elemene (ELE) is locally loaded in β-CD with high loading efficiency (8.72%) and encapsulation efficiency (78.60%) through hydrophobic desolvation and host–guest interaction. Above UCST, the release of the loaded ELE is accelerated to 72.87% in 24 h, together with the enhanced sensitization effect of synergized radiotherapy. Given spontaneous long-lasting delivery, targeted embolization, and post-treatment removal of such UCST-type submicrocage, it is anticipated to provide a novel, facile, efficient, and versatile strategy of comprehensive anticancer treatments for high drug bioavailability.