Hybrid Extracellular Vesicles‐Liposomes Camouflaged Magnetic Vesicles Cooperating with Bioorthogonal Click Chemistry for High‐Efficient Melanoma Circulating Tumor Cells Enrichment

Abstract

The capture of melanoma circulating tumor cells (melanoma CTCs, MelCTCs) is of great significance for the early diagnosis and personalized treatment of melanoma. The rarity and heterogeneity of MelCTCs have greatly limited the development of MelCTCs capture methods, especially those based on immune/aptamer-affinity. Herein, an extracellular vesicles-camouflaged strategy is designed to functionalize the magnetic nanoparticles (Fe 3 O 4 ) and to generate magnetic vesicles (Fe 3 O 4 @lip/ev) with excellent antifouling and active tumor cell targeting properties. Combined with the bioorthogonal click chemistry, the engineered magnetic vesicles with dibenzocyclooctyne can be widely used to target and separate all the metabolically labeled CTCs with varied phenotypes, organ origin, and even the biological species. The capture efficiency exceeded 80% with an extremely low detection limitation of ten cells. Most importantly, the strategy proposed can be directly applied to enrich MelCTCs from 0.5 mL blood samples of melanoma-bearing mice, with a greatly minimized residue of white blood cells (only 21-568) while ignoring the fluctuations of MelCTC phenotype.

Generally applicable circulating tumor cell enrichment and identification through a membrane glycoprotein–targeting strategy combining magnetic isolation and biological orthogonality labeling

“…Therefore, further research is imperative to validate the accuracy and universality of our strategy. Considering the fact that this strategy has been employed to selectively label the EpCAM-negative mouse melanoma cells with varied invasive performance (B16 and B16-F10) and EpCAM-positive mouse breast cancer 4T1 cells in our previous studies, 30 it is believed that the membrane glycoprotein–targeting strategy can be employed as a convenient and reliable tool to identify the captured tumor cells while ignoring their phenotype fluctuation, organ origin or even species diversity. More importantly, in view of the above-mentioned cellular functional analyses of the CTCs underwent successive capture and labeling, the membrane glycoprotein–targeting strategy would barely affect the activity of the identified CTCs, facilitating potential downstream CTC-related studies, likely the drug sensitivity testing and the construction of tumor-bearing animal models.…”

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors

“…The combination of these strengths will result in greater efficacy, including increased drug loading, natural active targeting, and immune system modulation, improving anti-tumor effects. In addition to the above, many engineering strategies can enhance tumor cell killing using such nanomaterials, including magnetic targeting [ 74 ], ligand-receptor binding [ 75 ], and bioorthogonal click chemistry [ 74 ].…”

Comparison of immunotherapy mediated by apoptotic bodies, microvesicles and exosomes: apoptotic bodies’ unique anti-inflammatory potential

“…They further extrude these hybrid vesicles with superparamagnetic ferroferric oxide nanoparticles to achieve magnetism and then insert 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[dibenzocyclooctyl(polyethylene glycol) (DSPE-PEG-DBCO).The DBCO-combined nanoparticle can capture circulating melanoma cells by azide-DBCO recognition. Than the captured melanoma cells can be enriched by magnetism [ 117 ]. Generally, the EV membrane in this research plays a role in camouflage to escape the recognition by MPS.…”