Abstract

BackgroundsMicrowave sensitization nanoplatform, integrating multiple functional units for improving tumor selectivity, is of great significance for clinical tumor microwave treatment. Lanthanide europium metal organic framework (EuMOF) is expected to be a theranostic nanoplatform owing to its unique luminescent and microwave sensitization properties. However, it is difficult to be applied to complicated biological systems for EuMOF due to its rapid degradation induced by the solvent molecular and ionic environment. In this work, a luminescent EuMOF nanocomposite (EuMOF@ZIF/AP-PEG, named EZAP) was designed, which brought the multifunctional characteristics of microwave sensitization, fluorescence imaging and drug loading.ResultsLamellar EuMOF was synthesized by a hydrothermal method. Through the charge adsorption mechanism, the zeolite imidazole framework (ZIF) structure was intensively assembled on the surface of EuMOF to realize the protection. Then, through in-situ Apatinib drug loading and PEG modification, EZAP nanocomposite was finally obtained. Apatinib (AP) was a kind of chemotherapy drug approved by Food and Drug Administration for targeted therapy of tumors. PEG modification increased long-term circulation of EZAP nanocomposite. The physical and chemical structure and properties of EuMOF@ZIF (EZ) were systematically represented, indicating the successful synthesis of the nanocomposite. The toxic and side effects were negligible at a safe dose. The growth of human liver cancer cells and murine liver cancer cells in vitro was significantly inhibited, and the combined microwave-thermal therapy and chemotherapy in vivo achieved high anti-cancer efficacy. Moreover, EZAP nanocomposite possessed bright red fluorescence, which can be applied for tumor imaging in tumor-bearing mice in vivo.ConclusionTherefore, EZAP nanocomposite showed high microwave sensitization, excellent fluorescence properties and outstanding drug loading capacity, establishing a promising theranostic nanoplatform for tumor therapy and fluorescence imaging. This work proposes a unique strategy to design for the first time a multifunctional nanoplatform with lanthanide metal organic frameworks for biological applications in tumor therapy and diagnosis.Graphical

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