Electrical-Charge-Mediated Cancer Cell Targeting via Protein Corona-Decorated Superparamagnetic Nanoparticles in a Simulated Physiological Environment

Abstract

A critical issue in nanomedicine is on the understanding of nano−bio interface behaviors, particularly when the nanoparticles are inevitably decorated by protein coronas in the physiological fluids. In this study, the effects of particle surface corona on cancer cell targeting were investigated in simulated physiological fluids. Cell targeting was achieved by two strategies: (1) using conventional epithelial cell adhesion molecule antibody-functionalized Fe 3 O 4 nanoparticles and (2) rendering the same but naked magnetic nanoparticles electrically positively charged, enabling them to electrostatically bind onto the negatively charged cancer cells. The cell-particle electrostatic binding was found to be much stronger with faster reaction kinetics than the immunological interactions even at 4 nC. Both types of nanoparticles were decorated with various protein coronas by administration in a simulated physiological system. Well-decorated by protein coronas, the electrically charged particles retained strong electrostatic interactions with cancer cells, even upon reversal of the particle zeta potential from positive to negative. This behavior was explained by a nonuniform corona modulation of the particle surface charge distributions, exposing locally positively charged regions, capable of strong electrostatic cell binding and magnetic capturing in a physiological environment. This fundamental discovery paves new way for sensitive detection of circulating tumor cells in whole blood in clinical settings.

Bioelectricity, Its Fundamentals, Characterization Methodology, and Applications in Nano‐Bioprobing and Cancer Diagnosis

“…Based on FBS coated magnetic nanoparticles, the net negative charge was −49 mV when the nanoparticles were further modified by polystyrene sulfonic (PSS), leading to negligible binding to the cancer cells. (Figure C) These results indicate, on the surface of FBS modified nanoparticle, the residue of positively‐charged patches could be completely enclosed by the small molecular weight anionic polyelectrolyte.…”

“…Several new characterization techniques have been emerging on studies of protein corona formation on nanoparticles . To investigate the effect of the nano‐surface‐decorated‐protein‐coronas on their cancer cells binding efficacy, we synthesized the positively and negatively charged magnetic nanoparticles that were treated with fetal bovine serum solution at different concentrations . Dozens of proteins in the serum were found to decorate either positive or negative surfaces of the nanoparticles, as characterized by Liquid Chromatography‐Mass Spectrometers (LC‐MS).…”

Molecular Programming of Biodegradable Nanoworms via Ionically Induced Morphology Switch toward Asymmetric Therapeutic Carriers

“…As already mentioned, high aspect‐ratio nanostructures are exciting targets for nanomedical investigation due to their improved biological performance and ability to enhance interactions with living cells . In particular, the ability to direct nanoparticles toward cancer cells, which typically possess more negative surface charge, using electrostatic targeting is an application deserving further investigation as a general strategy to increase the specificity of anticancer therapies 17a,24. With this in mind, we undertook preliminary testing to explore the advantageous properties of NWs comprising TerP 22 ‐Q 11 , comparing them to SMs and an uncharged nanoparticle control system (UPs), comprising PEG 22 ‐PCL 30 g TMC 30 .…”

Development and Characterization of Fe3O4@Carbon Nanoparticles and Their Biological Screening Related to Oral Administration

“…Of great interest to most researchers dealing with nanotechnology science are nanoparticles due to the fact that the most of the research works reported in the literature have focused to interconnect the engineered science of these nanomaterials with medical problems. Nanoparticles are broadly used in all areas of medicine from drug development [5][6][7] to magnetic resonance imaging and hyperthermia for the treatment of cancer [8][9][10][11], targeted drug delivery [12,13], computer tomograf (CT) and optical imaging [14,15], cellular therapy [16,17], tissue repair [18], and gene manipulations [19,20].…”