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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.

Isolation of circulating tumor cells (CTCs) in peripheral blood from cancer patients bears critical importance for evaluation of therapeutic efficacy. The current CTC isolation strategies are majorly relying on either protein biomarkers or dimensional features of CTCs. In this study, we present a new methodology for CTC detection and isolation based on the surface charge of cancer cells, a bioelectrical manifestation of the “Warburg effect.” Negative surface charge is a direct consequence of glycolysis of cancer cells, which can be utilized as an effective biophysical marker for CTC detection and isolation. Upon cancer cells–nanoparticle interaction via optimum incubation, serum protein-coated electrically charged nanoparticles can trap different cancer cells independent of their epithelial protein expression. In fetal bovine serum , the poly­(ethyleneimine)-functionalized Fe3O4 nanoparticles, surface-decorated with protein corona, are able to efficiently capture CTCs from blood samples of colorectal cancer patients.  2–8 CTCs has been isolated from 1 mL of blood and identified by immunostaining fluorescence in situ hybridization and immunofluorescence staining in all 25 colorectal cancer patients at varied stages, while only 0–1 CTC was detected from blood samples of 10 healthy donors. Diverse CTC subpopulations of heteroploids and biomarker expression can also be detected in this strategy. The label-free, charge-based CTC method shows promise in cancer diagnosis and prognosis paving a new path for liquid biopsy.

Although inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor‐made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half‐life time (≈1 µs). Developing a novel nanocatalyst platform involving longer half‐life time ROS is desired. To this end, Fe3O4‐Schwertmannite nanocomposites (Fe3O4‐Sch) with triple‐effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the •OH produced by Fe3O4 via the Fenton reaction into sulfate radicals with a longer half‐life time (30 µs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the l‐buthionine sulfoximine (BSO) molecules loaded in the hollow Fe3O4 cores. The comprehensive properties of the nanoplatform including the dual‐radical production, Fe3O4 nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.

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