Chemo-immunotherapy by dual-enzyme responsive peptide self-assembling abolish melanoma

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Cancer cells exhibit unique enzyme expression profiles.
• Targeted drug delivery remains a challenge in cancer treatment.
• Chemo-immunotherapy offers a promising strategy for enhanced anti-tumor effects.

Purpose of the Study:

• To design a nanomedicine that responds to dual enzyme markers for selective cancer cell targeting.
• To develop a chemo-immunotherapy strategy utilizing enzyme-responsive peptide self-assembly.
• To evaluate the in vitro and in vivo efficacy of the dual-enzyme responsive nanomedicine.

Main Methods:

• Designed a nanomedicine responsive to alkaline phosphatase and matrix metalloproteinase 2.
• Utilized enzyme-mediated self-assembly for targeted release of immune molecules and chemotherapeutics.
• Investigated cancer cell selectivity using B16-F10, CT26, MCF-7, and LO2 cell lines.
• Performed in vivo studies to assess anti-tumor efficacy and immune response.

Main Results:

• The nanomedicine demonstrated selective drug release and self-assembly in cancer cells expressing both target enzymes.
• Achieved efficient delivery of chemotherapeutics (HCPT) and immune molecules (IND).
• Demonstrated lysosomal escape and induction of cancer cell apoptosis.
• In vivo studies showed enhanced chemo-immunotherapy, elevated pro-inflammatory cytokines, and significant tumor growth inhibition.

Conclusions:

• The dual-enzyme responsive nanomedicine exhibits high selectivity for malignant cancer cells.
• This strategy effectively combines chemotherapy and immunotherapy for potent anti-tumor effects.
• The developed nanomedicine provides a versatile platform for novel multifunctional anti-tumor nanomedicines.