Drug-Free Approach to Regulate Undruggable Proto-Oncogene MYC Using Biomimetic Porous Nanoparticles for Cancer...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• The MYC proto-oncogene is critical for immune response but remains undruggable, with existing inhibitors showing limited efficacy and high toxicity.
• Drug-free strategies for MYC regulation are underexplored, presenting a significant gap in cancer treatment research.
• Developing novel therapeutic approaches to target MYC is essential for advancing cancer immunotherapy.

Purpose of the Study:

• To investigate the potential of drug-free photothermal therapy (PTT) in regulating the MYC proto-oncogene.
• To evaluate the efficacy of biomimetic black porous silicon (BPSi) nanoparticles in PTT-mediated MYC regulation.
• To explore the underlying mechanisms and in vivo therapeutic effects of PTT-induced MYC modulation for cancer treatment.

Main Methods:

• Synthesis of biomimetic black porous silicon (BPSi) nanoparticles coated with cancer cell membrane and polyethylene glycol.
• Application of PTT using BPSi nanoparticles at controlled temperatures (46°C and 50°C) to treat tumors.
• Analysis of MYC expression levels, downstream targets ('MYC Targets V1'), and signaling pathways (MAPK, JAK-STAT).
• In vivo assessment of tumor growth inhibition and toxicity in a tumor-bearing model.

Main Results:

• BPSi nanoparticles demonstrated efficient photothermal conversion, biocompatibility, and tumor targeting.
• PTT at 50°C successfully inhibited MYC expression, whereas PTT at 46°C upregulated it.
• MYC inhibition was linked to the downregulation of 'MYC Targets V1' and involvement of MAPK and JAK-STAT pathways.
• Tumor-targeted PTT at 50°C activated cancer immunotherapy, prevented tumor growth, and showed no significant in vivo toxicity.

Conclusions:

• Drug-free PTT using BPSi nanoparticles can effectively regulate MYC expression by precise temperature control.
• Targeted PTT offers a promising strategy for MYC inhibition, leading to enhanced cancer immunotherapy.
• This approach holds potential for developing potent and less toxic cancer therapies by modulating MYC.