Biotin-Targeted Nanomicellar Formulation of an Anderson-Type Polyoxomolybdate: Synthesis and In Vitro Cytotoxicity Evaluations

Abstract

This study is aimed at developing a micellar carrier for an Anderson-type manganese polyoxomolybdate (TRIS-MnPOMo) to improve the potency and reduce the general toxicity. The biotin-targeted stearic acid–polyethylene glycol (SPB) polymeric conjugate was selected for the first time as a micelle-forming basis for the delivery of TRIS-MnPOMo to breast cancer cells. The cytotoxicity of TRIS-MnPOMo and its nanomicellar form (TRIS-MnPOMo@SPB) was evaluated against MCF-7, MDA-MB-231 (breast cancer cell lines), and HUVEC (normal cell line) in vitro using the MTT assay. The quantity of cellular uptake and apoptosis level were studied properly using standard methods. The hydrodynamic size, zeta potential, and polydispersity index of the prepared micelles were 140 nm, −15.6 mV, and 0.16, respectively. The critical micelle concentration was about 30 μg/mL, which supports the colloidal stability of the micellar dispersion. The entrapment efficiency was interestingly high (about 82%), and a pH-responsive release of TRIS-MnPOMo was successfully achieved. The micellar form showed better cytotoxicity than the free TRIS-MnPOMo on cancer cells without any significant heme and normal cell toxicity. Biotin-targeted nanomicelles internalized into the MDA-MB-231 cells interestingly better than nontargeted micelles and TRIS-MnPOMo, most probably via the endocytosis pathway. Furthermore, at the same concentration, micelles remarkably increased the level of induced apoptosis in MDA-MB-231 cells. In conclusion, TRIS-MnPOMo@SPB could profoundly improve potency, safety, and cellular uptake; these results are promising for further evaluations in vivo.

Hierarchy of Complex Glycomacromolecules: From Controlled Topologies to Biomedical Applications

“…While passively targeted drug delivery to tumor cells can be achieved by exploiting the enhanced permeability and retention (EPR) effect, 170,171 nanocarriers with targeting functionalities offer a versatile way to deliver cargo to a specific cell type expressing the corresponding receptors. Targeting can be mediated by either nanoparticle size 172 or ligands for selective recognition such as antibod- ies, 173,174 folic acid, 175,176 biotin, 177,178 peptides, 179,180 hormones, 181,182 and carbohydrates. 183 Glycosylated ligands are utilized in targeted delivery systems because of the highly specific interaction between carbohydrates and their lectin counterparts.…”

Mechanism of CK2 Inhibition by a Ruthenium-Based Polyoxometalate

“…In this way, biomedical studies could be performed on POMs stable in solution, employing physiological conditions and concentrations ( Čolović et al, 2020 ). The derivatization of POMs may increase both stability and bioavailability, while providing interesting opportunities for tracking and targeting ( Zamolo et al, 2018 ; Ramezani-Aliakbari et al, 2021 ; Tagliavini et al, 2021 ).…”