Interfacial Polymerization Produced Magnetic Particles with Nano‐Filopodia for Highly Accurate Liquid Biopsy in the PSA Gray Zone

Abstract

Magnetic particles are leading separation materials for biological purification and detection. Existing magnetic particles, which almost rely on molecule‐level interactions, however, often encounter bottlenecks in highly efficient cell‐level separation due to the underestimate of surface structure effects. Here, immune cell‐inspired magnetic particles with nano‐filopodia (NFMPs) produced by interfacial polymerization for highly efficient capture of circulating tumor cells (CTCs) and further accurate clinical diagnosis of prostate cancer are reported . The unprecedented construction of nano‐filopodia on polymer‐based magnetic particles is achieved by introducing electrostatic interactions in emulsion interfacial polymerization. Due to the unique nano‐filopodia, the NFMPs allow remarkably enhanced CTCs capture efficiency (86.5% ± 2.8%) compared with smooth magnetic particles (SMPs, 35.7% ± 5.7%). Under the assistance of machine learning by combining with prostate‐specific antigen (PSA) and free to total PSA (F/T‐PSA), the NFMPs strategy demonstrates high sensitivity (100%), high specificity (93.3%), and a high area under the curve (AUC) value (98.1%) for clinical diagnosis of prostate cancer in the PSA gray zone. The NFMPs are anticipated as an efficient platform for CTCs‐based liquid biopsy toward early cancer diagnosis and prognosis evaluation.

Heterostructured Microparticles: From Emulsion Interfacial Polymerization to Separation Applications

“…Except for molecule separation, the heterostructured microparticles also exhibit significant advantages for cell separation. The nanofractal magnetic microparticles have demonstrated much enhanced CTCs capture efficiency compared with smooth magnetic microparticles (Figure a) . The nanofractal magnetic microparticles show a similar surface structure with immune cells.…”

“…As a general approach to synthesizing heterostructured microparticles, emulsion interfacial polymerization is applicable to a wide range of hydrophilic monomers (Table ). For example, acrylamide (AM), N -isopropylacrylamide (NIPAM), methacrylamide (MAM), hydroxyethyl acrylate (HEA), maleic anhydride (MAH), hydroxyethyl methacrylate (HEMA), AA, maleic acid (MA), and itaconic acid (IA) are applicable for the synthesis of Janus microparticles. ,,, AM, ethylene glycol dimethacrylate (EGDMA), HEMA, N , N ’-methylene bis­(acrylamide) (MBA), AA, ethylene glycol monoallyl ether (EGMAE), SS, and 2-trimethylammoniumethyl methacrylate chloride (TMAEMC) are applicable for the synthesis of heterostructured porous microparticles. ,,− SS, SVBZ, and SVPB are applicable for the synthesis of nanofractal microparticles. ,, To date, most research has been concentrated on the regulation of hydrophilic polymers, and rare attention has been paid to the regulation of hydrophobic polymers. In fact, vinyl-containing monomers that can be initiated by free radicals are expected to be suitable for emulsion interfacial polymerization owing to the polymerization mechanism .…”

“…The CTCs can stretch out many long filopodia to grab the nanofractal magnetic microparticles, while much fewer and shorter filopodia are observed for smooth magnetic microparticles. Reproduced with permission from ref . Copyright 2023 Wiley-VCH.…”

“…Third, the hydrophilic PAA surface can also be modified with fluorescently labeled proteins via covalent bonding interaction mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/ N -hydroxysuccinimide (NHS) activation (Figure c). In addition to surface functionalization, hydrophobic magnetic Fe 3 O 4 NPs can also be incorporated into the hydrophobic part of the heterostructured microparticles when they were mixed with the hydrophobic monomers before emulsion interfacial polymerization. , The wide tunability of surface chemistry and functionalization endows heterostructured microparticles with prominent capability for the separation of species with varied physical and chemical properties.…”