Targeting and disrupting cytoskeleton using core-shell metal-organic framework nanoparticles to inhibit cancer cell...

Area of Science:

• Nanotechnology
• Cancer Biology
• Materials Science

Background:

• Cancer metastasis is driven by cancer cell motility, regulated by the actin cytoskeleton.
• Current actin-disrupting drugs lack selectivity and cause off-target effects.
• Targeting migration-associated surface markers is a strategy to improve drug specificity.

Purpose of the Study:

• To develop core-shell metal-organic framework nanoparticles for targeted disruption of the actin cytoskeleton in migratory cancer cells.
• To investigate the efficacy of EpCAM antibody-functionalized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs@Ab) in inhibiting cancer cell migration and invasion.
• To elucidate the mechanisms underlying nanoparticle-mediated cytoskeletal disruption.

Main Methods:

• Fabrication of core-shell zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) functionalized with EpCAM antibodies.
• In vitro assessment of nanoparticle treatment on breast and prostate cancer cell migration and invasion.
• Single-cell imaging and mechanistic investigations to analyze actin cytoskeleton disruption and nanoparticle synergistic effects.

Main Results:

• ZIF-8 NPs@Ab significantly inhibited migration and invasion of breast and prostate cancer cells at low doses.
• Actin cytoskeleton disruption was identified as the mechanism underlying the inhibition of cell migration.
• Synergistic effects between the degradable ZIF-8 core and EpCAM-targeted antibody shell contributed to cytoskeletal disruption.

Conclusions:

• EpCAM-targeted ZIF-8 NPs provide a versatile and effective strategy for inhibiting cancer cell motility.
• This nanoparticle system demonstrates potential for safer cancer treatment by specifically targeting migratory cancer cells.
• The approach holds promise for developing novel therapeutics against metastasis by targeting cancer cell migration.