Abstract
Development of safer nanomedicines for drug delivery applications requires immense efforts to improve clinical outcomes. Targeting a specific cell, biocompatibility and biodegradability are vital properties of a nanoparticle to fulfill the safety criteria in medical applications. Herein, we fabricate antibody-functionalized carnauba wax nanoparticles encapsulated a hydrophobic drug mimetic, which is potentially interesting for clinical use due to the inert and nontoxic properties of natural waxes. The nanoparticles are synthesized applying miniemulsion methods by solidifying molten wax droplets and further evaporating the solvent from the dispersion. The pH-selective adsorption of antibodies (IgG1, immunoglobulin G1, and CD340, an antihuman HER2 antibody) onto the nanoparticle surface is performed for practical and effective functionalization, which assists to overcome the complexity in chemical modification of carnauba wax. The adsorption behavior of the antibodies is studied using isothermal titration calorimetry (ITC), which gives thermodynamic parameters including the enthalpy, association constant, and stoichiometry of the functionalization process. Both antibodies exhibit strong binding at pH 2.7. The CD340-decorated wax nanoparticles show specific cell interaction toward BT474 breast cancer cells and retain the targeting function even after 6 months of storage period.
Highlights
Multifunctional nanocarriers are vital tools to develop safer nanomedicines for drug delivery applications.[1]
We demonstrated the development of antibodyfunctionalized carnauba wax nanoparticles and their further use in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells
Since the adsorption was optimum at acidic conditions acquired from flow cytometry analysis, thermodynamic characteristics of this functionalization process were studied at pH 2.7 and 6.1 using isothermal titration calorimetry (ITC)
Summary
Multifunctional nanocarriers are vital tools to develop safer nanomedicines for drug delivery applications.[1]. To remove the heat of dilution effects, titration of antibodies into the corresponding buffer solution was performed and subtracted from the heat changes of the main titration before the independent binding fits BT474 human breast cancer cells are characterized by the overexpression of human epidermal growth factors receptor 2 (HER2).[37,38] Figure 3 shows the flow cytometry histograms of BT474 cells, wherein time- and concentration-dependent uptake of the antibody-functionalized carnauba wax nanoparticles was demonstrated. Conservation of the functions for a relatively high time period is a significant success of the developed nanoparticles that enables us to define the limits of the shelf life for complex and costly medical applications
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