A novel Granzymes and miRNA nanocapsules co-delivery system for tumor suppression

Area of Science:

• Biomedical Engineering
• Cancer Therapy
• Nanotechnology

Background:

• Granzymes immunotherapy shows promise for solid tumors but requires improvement due to cancer cell evasion and metastasis.
• Current limitations in Granzyme-based therapies necessitate novel strategies to enhance efficacy against aggressive cancers like breast cancer.

Purpose of the Study:

• To investigate the synergistic anti-tumor effect of Granzyme B (GrB) and miR-21 inhibitor (miR-21i) for breast cancer therapy.
• To develop and evaluate a novel co-delivery system for simultaneous GrB and miR-21i delivery.

Main Methods:

• GrB was covalently bonded with miR-21i via a disulfide bond.
• Co-delivery system constructed using N-(3-aminopropyl) methacrylamide (APM), ethylene glycol dimethacrylate (EGDMA), and 2-Methacryloyloxyethyl phosphorylcholine (MPC) for nanocapsule formation.
• In vitro assays (MTT, flow cytometry, transwell invasion) and in vivo mouse tumor models were used to assess therapeutic efficacy.

Main Results:

• The developed nanocapsules exhibited spherical morphology, uniform size, and pH responsiveness.
• Co-delivery of GrB and miR-21i demonstrated synergistic anti-proliferation and apoptosis-promoting effects in breast cancer cell lines.
• The nanocapsules significantly inhibited cancer cell invasion and showed potent in vivo anti-tumor efficacy in a mouse model.

Conclusions:

• The novel nanocapsules effectively co-deliver Granzyme B and miR-21 inhibitor, producing a synergistic therapeutic effect.
• This combinatorial approach holds significant potential for improving breast cancer treatment by overcoming drug resistance and metastasis.