pH-Responsive Charge-Conversional and Hemolytic Activities of Magnetic Nanocomposite Particles for Cell-Targeted Hyperthermia

Abstract

Magnetic nanocomposite particle (MNP)-induced hyperthermia therapy has been restricted by inefficient cellular targeting. pH-responsive charge-conversional MNPs can enhance selective cellular uptake in acidic cells like tumors by sensing extracellular acidity based on their charge alteration. We have synthesized new, pH-induced charge-conversional, superparamagnetic, and single-cored Fe3O4 nanocomposite particles coated by N-itaconylated chitosan (NICS) cross-linked with ethylene glycol diglycidyl ether (EGDE) (Fe3O4-NICS-EGDE) using a simple, one-step chemical coprecipitation–coating process. The surface of the Fe3O4-NICS-EGDE nanocomposite particles was modified with ethanolamine (EA) via aza-Michael addition to enhance their buffering capacity, aqueous stability, and pH sensitivity. The designed Fe3O4-NICS-EGDE-EA nanocomposite particles showed pH-dependent charge-conversional properties, colloidal stability, and excellent hemocompatibility in physiological media. By contrast, the charge-conversional properties enabled microwave-induced hemolysis only under weakly acidic conditions. Therefore, the composite particles are highly feasible for magnetically induced and targeted cellular thermotherapeutic applications.

A facile aqueous production of bisphosphonated-polyelectrolyte functionalized magnetite nanoparticles for pH-specific targeting of acidic-bone cells

“…The z-potentials were decreased as the increase of the pH values due to the partial deprotonation of the ammonium structure transforming into the amine groups. The weakly positive z-potentials in this precipitating region, not isoelectric and higher than those of our previously reported material 56 implies that a part of the cationic groups does not contribute to the precipitation behavior. A plausible reason is the lower concentration of the free bisphosphoric and carboxyl groups around the surface contributing to the ionic crosslinkage due to the ligation to the Fe 3 O 4 core as suggested by the FTIR spectroscopic study.…”

“…The hemolysis degrees of Fe 3 O 4 -NCCS-FITC-AL are signicantly lower than that of previously reported magnetic nanocomposite particles coated with cationic polyelectrolyte, 48 carboxy-CS, 28 and functionalized carboxy-CS. 56 The morphological change of the sheep erythrocytes in the presence and absence of Fe 3 O 4 -NCCS-FITC-AL was conrmed by optical microscopy (Fig. 6B).…”

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…These polymers show this mixed behavior due to the presence of both acidic and basic functional groups, which change their protonation status during endosomal acidification. Rahman and colleagues developed N-itacolynated chitosan-coated IONs crosslinked with ethylene glycol diglycidyl ether (NICS-EGDE-IONs), which had both carboxylate and amine moieties, and demonstrated high endosomal escape mainly due to their capacity to induce the proton-sponge effect in acidic environments [ 282 ]. Similarly, polycations conjugated with anionic moieties through acid-cleavable linkages exhibit response to endosomal acidification.…”

A facile one-pot synthesis of poly(acrylic acid)-functionalized magnetic iron oxide nanoparticles for suppressing reactive oxygen species generation and adsorption of biocatalyst

“…Nowadays, the study of iron oxide nanoparticles (IONPs) is of great interest because of their potential biomedical applications including magnetic drug delivery, tumor-specific cell targeting, biosensor, magnetic resonance imaging, hyperthermia and bioseparation [1][2][3][4][5][6][7][8]. One of the most exciting properties of IONPs is magnetism, which allows them to be guided and stimulated to a desired site of the biological system by using an external magnet.…”