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-B urman 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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, a core-shell metal organic framework (MOF) of zinc was developed with titanocene dichloride (TC) loaded lactoferrin (Lf) as the core. Various experimental techniques were used to study the complexation of TC to Lf, and optimization of size and yield of Lf-TC NPs was achieved through different design methods. The developed nanoplatform showed potential for multimodal therapy of Neuroblastoma by loading anti-cancer drug 5 Fluorouracil inside ZIF-8 framework.