A Three-in-One Nanoscale Coordination Polymer for Potent Chemo-Immunotherapy

Area of Science:

• Nanotechnology
• Cancer Research
• Immunotherapy

Background:

• Chemo-immunotherapy improves cancer care but has limited efficacy in colorectal and triple-negative breast cancers.
• Developing novel strategies is crucial for treating advanced and aggressive cancers.

Purpose of the Study:

• To design and evaluate a three-in-one nanoscale coordination polymer (NCP) for triple-modality chemo-immunotherapy.
• To investigate the therapeutic potential of OX/GC/CQ in preclinical cancer models.

Main Methods:

• Synthesized a nanoscale coordination polymer (NCP) loaded with oxaliplatin (OX), gemcitabine (GC), and 5-carboxy-8-hydroxyquinoline (CQ).
• Evaluated pharmacokinetics, tumor accumulation, and drug release of OX/GC/CQ.
• Assessed the immunogenic cell death, immune cell infiltration, and regulatory T cell proportions.
• Tested the efficacy of OX/GC/CQ in reducing tumor growth, metastasis, and improving survival in mouse models of colorectal and triple-negative breast cancer.

Main Results:

• OX/GC/CQ demonstrated optimal pharmacokinetics and enhanced drug release in acidic tumor tissues.
• CQ significantly boosted immunogenic cell death and downregulated PD-L1 expression.
• OX/GC/CQ promoted cytotoxic T lymphocyte infiltration and activity while reducing immunosuppressive regulatory T cells.
• Intravenous administration of OX/GC/CQ reduced tumor growth, prevented lung metastasis, and extended survival by 30-40 days.

Conclusions:

• NCPs offer a promising platform for co-delivering synergistic chemo-immunotherapeutics.
• OX/GC/CQ demonstrates significant therapeutic potential for advanced and aggressive cancers.
• This approach warrants further investigation for clinical translation.