Biomarkerless targeting and photothermal cancer cell killing by surface-electrically-charged superparamagnetic Fe₃O₄composite nanoparticles

Abstract

A major challenge in cancer therapy is localized targeting of cancer cells for maximum therapeutic effectiveness. However, due to cancer heterogeneities, the biomarkers are either not readily available or specific for effective targeting of cancer cells. The key, therefore, is to develop a new targeting strategy that does not rely on biomarkers. A general hallmark of cancer cells is the much increased level of glycolysis. The loss of highly mobile lactate from the cytoplasm inevitably removes labile inorganic cations to form lactate salts and acids as part of the lactate cycle, creating a net of negative surface charges. This net of negative charges on cancer cell surfaces biophysically distinguishes themselves from normal cells. In this study, cancer cells are targeted by using positively-charged, fluorescent, superparamagnetic FeO-composite nanoparticles. The positively-charged FeO composite nanoparticles bind predominantly to cancer cells due to their negatively-charged surfaces. Upon electrical-charge-mediated FeO nanoparticle binding onto cancer cells, irradiation by using an 808 nm laser is subsequently applied to induce photothermal hyperthermia that kills the cancer cells directly. The negatively-charged composite nanoparticles are found, however, not to target and bind the cancer cells due to the electrostatic repulsive force between them. This unique strategy paves a new path for effective targeting and direct cancer cell killing without relying on any biomarkers and anticancer drugs.

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

“…Various charged‐nanoprobes have been designed for multiple purposes: 1) detection and isolation of CTCs, and 2) cancer cell killing by the photothermal effects of the magnetic nanoprobes, since these nanoprobes are not only electrically charged (positive or negative), but also superparamagnetic . Therefore, in addition to cancer cell detection and insulation, effective HeLa cell ablation has also been achieved in vitro utilizing the photothermal effect of the magnetic nanoprobes.…”

Natural cancer-killing activity of human granulocytes

“…All tested cancer cells bound exclusively to the positive NPs (Figure 3, previously published [61]). Except for granulocytes, normal cells had no binding to either type of NPs [61,62]. The negative surface charges are highly sensitive to inhibition of glycolysis and are generated as a result of lactate secretion.…”

Cancer Cell Surface Negative Charges: A Bio-Physical Manifestation of the Warburg Effect

“…1. [9][10][11][12] When mixing the positively-charged nanoprobes with cancer cells of any type, they massively bind onto the cell surfaces due to opposite electrical charges. 10 As shown in Fig.…”

“…[9][10][11][12] When mixing the positively-charged nanoprobes with cancer cells of any type, they massively bind onto the cell surfaces due to opposite electrical charges. 10 As shown in Fig. 2, the green°uorescence from the positivelycharged nanoparticles (MNCsÈÞ is visible around the cancer cells (the blue colored cell nucleus is stained by DAPI) due to strong electrostatic force (middle column in Fig.…”

“…2). 10 In sharp contrast, no green°uorescence can be observed on the membrane of cancer cells treated by the negativelycharged nanoparticles (MNCs ÂÞ. These are strong experimental evidences that show the negativelycharged cancer cell surfaces, consistent with the hypothesis based on the Warburg E®ect.…”