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Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal–organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH2-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.

Magnetic nanomaterials (MNMs) have a wide range of applications in the fields of pharmaceutical sciences, medicine, catalysis, and electronics. A specific set of physical and chemical properties controls the applicability of the developed MNMs to their intended use. These properties include the size, charge, zeta potential, morphology, and magnetic behavior of the designed MNMs. The aforementioned properties are addressed in this chapter, along with the MNMs classification. The MNMs synthesis method can modulate their characteristics including high saturation field, superparamagnetic behavior, high field irreversibility, and extra anisotropy contribution. Thus the second part of this chapter highlights a variety of synthetic routes to develop MNMs. Furthermore, the quality determinants of MNMs are their surface modifications, which mostly impart MNMs with novel chemical and physical stability as well as enhanced molecular affinity. Accordingly, the coating materials to stabilize MNMs as well as the various functionalization techniques are also covered.

Background: Hydrogen peroxide is a key component of fungal biomass degradation. Fungal extracellular enzymes can produce this reactive oxygen species or depend on it as a co-substrate. The measurement of H2O2 in proximity of enzymes bound to biomass is important to elucidate its production rate by oxidases, its consumption rate by peroxidases. Objectives This work reports the fabrication and characterization of pencil graphite electrode (PGE) and its application to measure the H2O2 production by cellobiose dehydrogenase (CDH). Methods: The limit of detection (LOD) and the sensitivity of pencil graphite electrode were detected for both of bare and modified PGE, respectively. The H2O2 generation of cellulose immobilized CDH was measured using the MOF modified PGE. CDH produces H2O2 in the presence of cellobiose as a substrate. Results: MOF modified PGE exhibited low LODs (571 μM) and high sensitivities (2.35μA mM-1mm-1). The lower acquisition costs and higher simplicity compensate for the higher LODs and lower sensitivities when compared to platinum electrodes. Conclusions: PGE was easy to fabricate, multiply usable and cost effective which make it a strong and promising tool for H2O2 measuring.