Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery

Abstract Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe‐based metal‐organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe‐CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH‐triggered drug release 82% within 72 h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284 mg g −1 ). In addition to its potent chemotherapy attributes, Fe‐CP‐HoMS possesses chemodynamic therapy potential by continuously catalyzing H 2 O 2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S‐Fe‐CP‐HoMS, at a concentration of 12.5 µg mL −1 , demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP‐HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.