Optimized metal-organic-framework based magnetic nanocomposites for efficient drug delivery and controlled release*

Metal organic framework (MOF) has attracted wide attention as a promising biological platform due to its distinctive characteristics such as large surface areas, tunable pore sizes, and high selectivity in small molecule uptake. The incorporation of other guest materials into MOFs has resulted in additional functionalities of the conjugated MOF-composites. In this work, we have successfully conjugated Fe3O4 magnetic nanoparticles with MIL-88B-NH2 MOF structures using optimized synthetic media containing acetic acid as a modulating agent and F127 co-polymer as a stabilizing agent, which result in a well-controlled hybrid magnetic nanocomposite with an average size of 117 nm. This unique hybrid material has been further utilized as a nanocarrier for efficient drug delivery with the capability of on-demand controlled drug release. Glioblastoma drugs, including Carmustine (BCNU) and Mertansine (DM1), have been successfully loaded into the pores of the MOF structure to minimize their significant systemic toxic side effects that limit their clinical applications. Additionally, the controlled drug release was achieved through a localized heating effect produced by the magnetic nanodomains incorporated in the MOF structure after the application of an alternating magnetic field (AMF) on the DM1-loaded magnetic nanocomposites. In vitro cytotoxicity studies on U251 glioblastoma cells have been conducted to demonstrate the therapeutic efficacy of the drug delivery system and its capability of achieving on-demand drug release with the AMF as an external stimulus. Our results suggested that the fabricated magnetic nanocomposites are efficient for the controlled DM1 delivery, which exhibit superior cancer cell killing effects.