A combination of glioma in vivo imaging and in vivo drug delivery by metal–organic framework based composite nanoparticles

Abstract

The success of glioma chemotherapy is hampered by low intratumoral drug concentration and severe toxicity in normal organs. Glioma diagnosis and total tumor resection depend on enhanced magnetic resonance imaging (MRI) results which provide the best solution for recognizing tumor mass anatomical details with high spatial resolution. Zeolite imidazole frameworks (ZIFs) have pore channel tunability, large specific surface area and porosity, and have broad application prospects in adsorption, catalysis and drug loading. However, there are few reports on post-synthesis ZIF-8 based multifunctional nanocomposites as a theranostic agent for in vivo diagnostic and therapeutic applications simultaneously. In this study, we synthesized a low toxicity bimetallic zeolitic imidazolate framework (Mn-ZIF-8) with good dispersibility and high specific surface area, which could be used for potential high drug loading. Meanwhile, we used Mn-ZIF-8 for the first time for in vivo MRI. T₁-weighted MR signals at tumor sites continuously increased over time after injecting Mn-ZIF-8 intravenously. Moreover, 12 hours after injecting Mn-ZIF-8 into a nude mouse bearing U87-MG tumor, a relatively high accumulation of Mn²⁺ in tumors was observed, probably due to the EPR effect of cancerous tumors. Targeted delivery significantly improves the therapeutic efficacy of Mn-ZIF-8/5-Fu in U87-MG tumor-bearing mice, resulting in 80% survival rate over 40 days of treatment. Mn-ZIF-8/5-Fu has excellent in vivo biocompatibility at a given dose, which induces minimal side effects on the functions of important organs. Therefore, efficient 5-Fu loaded Mn-ZIF-8 with favorable in vivo biocompatibility, pH responsiveness and T₁-weighted contrast MRI of tumors can be used as a promising framework for diagnostic and therapeutic applications in the case of glioma simultaneously.