Transformable Helical Self-Assembly for Cancerous Golgi Apparatus Disruption

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• The Golgi apparatus plays a key role in cellular drug resistance.
• Developing strategies to overcome drug resistance in cancer is crucial.
• Nanoparticle-based therapies offer potential for targeted cancer treatment.

Purpose of the Study:

• To design a peptide-based nanostructure for targeted cancer cell disruption.
• To investigate the potential of nanomechanical disruption of the Golgi apparatus as a cancer therapy.
• To explore a novel approach to circumvent drug resistance in cancer treatment.

Main Methods:

• Design of a transformable peptide (C6RVRRF4KY) capable of self-assembly.
• Self-assembly into nanoparticles in aqueous media.
• Targeting and cleavage by furin within the Golgi apparatus of cancer cells, forming left-handed helical fibrils (L-HFs).
• Mechanical disruption of the Golgi apparatus membrane by L-HFs.

Main Results:

• Peptide self-assembles into nontoxic nanoparticles.
• Nanoparticles transform into L-HFs upon Golgi apparatus targeting and cleavage.
• L-HFs mechanically disrupt the Golgi apparatus membrane.
• Disruption leads to inhibition of cytokine secretion and cellular structure collapse, causing cancer cell death.
• No acquired drug resistance observed after repeated stimulation.

Conclusions:

• Nanomechanical disruption of the Golgi apparatus is a viable strategy for cancer therapy.
• This approach effectively kills cancer cells and overcomes drug resistance.
• The concept holds potential for treating multidrug-resistant bacteria and viruses.