ZIF-8 nano confined protein-titanocene complex core-shell MOFs for efficient therapy of Neuroblastoma: Optimization, molecular dynamics and toxicity studies.

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma.

Functional groups influence and mechanism research of UiO-66-type metal-organic frameworks for ketoprofen delivery.

UiO-66 metal-organic framework (MOF) was introduced as ketoprofen delivery system for treating osteoarthritis (OA), and two different kinds of NH2 and NO2 functional groups were grafted into the UiO-66 framework to investigate the effect of functional groups on the drug loading level and release rate. Structural characterization of the samples showed that grafting functional groups had no significant effect on the morphological characteristic and crystal structure of UiO-66. All synthesized MOFs carriers had excellent BET, chemical and thermal stability, though the introduction of NH2 and NO2 functional groups were detrimental for these characteristics. Ketoprofen was successfully loaded on the MOFs carriers, and the results of high performance liquid chromatography (HPLC) indicated UiO-66-NH2 had the highest loading amount (38%). The ketoprofen release experiment manifested that UiO-66-NH2 exhibited lowest release rate and partial release of ketoprofen (about 65%) even after 72 h due to the high hydrogen bonds capacity and alkaline characteristic of -NH2. Furthermore, chondrocyte cytotoxicity experiment manifested that the synthesized MOFs carriers were rather bio-safe, which ensured them to be used as the drug delivery vehicles.