Cell-Membrane-Coated and Cell-Penetrating Peptide-Conjugated Trimagnetic Nanoparticles for Targeted Magnetic Hyperthermia of Prostate Cancer Cells

Prostate malignancy represents the second leading causeof cancer-specificdeath among the male population worldwide. Herein, enhanced intracellularmagnetic fluid hyperthermia is applied in vitro totreat prostate cancer (PCa) cells with minimum invasiveness and toxicityand highly specific targeting. We designed and optimized novel shape-anisotropicmagnetic core-shell-shell nanoparticles (i.e., trimagneticnanoparticles - TMNPs) with significant magnetothermal conversionfollowing an exchange coupling effect to an external alternating magneticfield (AMF). The functional properties of the best candidate in termsof heating efficiency (i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4) were exploited following surface decoration with PCa cellmembranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstratedthat the combination of biomimetic dual CM-CPP targeting and AMF responsivenesssignificantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore,a downregulation of the cell cycle progression markers and a decreaseof the migration rate in surviving cells were observed in responseto the TMNP-assisted magnetic hyperthermia, suggesting a reductionin cancer cell aggressiveness.

Automated summary

Enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer cells with minimum invasiveness and toxicity. Novel shape-anisotropic magnetic core-shell-shell nanoparticles were designed and optimized, which showed significant magnetothermal conversion under an external alternating magnetic field. The best candidate, decorated with prostate cancer cell membranes and/or LN1 cell-penetrating peptide, induced apoptosis of prostate cancer cells and reduced cell aggressiveness.