A Biomimetic Nanoplatform Mediates Hypoxia-Adenosine Axis Disruption and PD-L1 Knockout for Enhanced MRI-Guided Chemodynamic-Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Malignant melanoma is an aggressive skin cancer with limited treatment options.
• Conventional therapies and current immunotherapies face challenges due to the immunosuppressive tumor microenvironment (TME).

Purpose of the Study:

• To develop a biomimetic nanoplatform (PPMC@CM) for enhanced melanoma treatment.
• To co-deliver CRISPR/Cas9-PD-L1 and manganese dioxide nanoparticles (MnO₂ NPs) for MRI-guided chemodynamic therapy (CDT) and immunotherapy.

Main Methods:

• Fabrication of cancer cell membrane-camouflaged nanoplatforms (PPMC@CM).
• Co-delivery of CRISPR/Cas9-PD-L1 system and MnO₂ NPs.
• Utilized homologous targeting, hypoxia relief, glutathione depletion, and MRI guidance.

Main Results:

• PPMC@CM efficiently accumulated at tumor sites, relieved hypoxia, and enhanced CDT via Fenton-like reactions.
• CRISPR/Cas9-mediated PD-L1 knockout and hypoxia relief boosted immunotherapy.
• In vivo studies showed significant inhibition of melanoma growth and metastasis with MRI guidance.

Conclusions:

• The PPMC@CM nanoplatform offers a novel theranostic strategy for melanoma.
• Combination of CDT and enhanced immunotherapy shows promise for treating aggressive melanoma.
• This approach addresses TME challenges and improves therapeutic outcomes.