Drug Delivery Platform Targeting MMP9 in Combination with Photothermal Therapy to Improve Tumor Chemosensitivity

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Tumor chemotherapy insensitivity is a major obstacle in cancer treatment.
• Angiogenesis, the formation of new blood vessels, supports tumor growth and impairs treatment efficacy.
• Matrix metalloproteinase-9 (MMP9) is often overexpressed in tumors and promotes angiogenesis.

Purpose of the Study:

• To develop a novel MMP9-responsive nanoplatform for overcoming chemotherapy insensitivity.
• To encapsulate methotrexate (MTX) and an MMP9 inhibitor (MMP9i) within carbon quantum dots (CQDs).
• To investigate the platform's ability to target tumors, release payloads, and inhibit angiogenesis and relevant signaling pathways.

Main Methods:

• Fabrication of an MMP9-responsive carbon quantum dot-based nanoplatform (MMP9i@MTX@CQDs).
• In vitro and in vivo studies to evaluate payload release, targeting, and therapeutic effects.
• Assessment of angiogenesis markers (VEGF, CD31) and the Wnt/β-catenin signaling pathway.
• Combination therapy involving chemotherapy, MMP9 inhibition, and photothermal therapy (PTT) via near-infrared (NIR) irradiation.

Main Results:

• The MMP9i@MTX@CQDs platform demonstrated MMP9-responsive drug release.
• NIR irradiation initiated photothermal therapy (PTT) and enhanced therapeutic effects.
• The nanoplatform effectively downregulated angiogenesis-related molecules (VEGF, CD31).
• Inhibition of the Wnt/β-catenin signaling pathway was observed, reversing chemotherapy insensitivity.

Conclusions:

• The developed nanoplatform successfully sensitizes tumors to chemotherapy by targeting angiogenesis and inhibiting MMP9.
• The integrated approach of chemotherapy, MMP9 inhibition, and PTT offers a promising strategy for cancer treatment.
• This nanoplatform presents a robust and safe method for enhancing the efficacy of cancer chemotherapy.