Codelivery of Que and BCL-2 siRNA with Lipid-Copolymer Hybrid Nanocomplexes for Efficient Tumor Regression

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Chemotherapy resistance in tumor cells, often due to abnormal gene overexpression, significantly reduces treatment efficacy.
• Targeted delivery of therapeutic agents is crucial for overcoming resistance and improving cancer treatment outcomes.

Purpose of the Study:

• To develop multifunctional nanocomplexes for synergistic delivery of quercetin (Que) and BCL-2 siRNA (siBCL2).
• To investigate the efficacy of these nanocomplexes in inhibiting tumor growth and metastasis in triple-negative breast cancer (TNBC).

Main Methods:

• Fabrication of amphiphilic triblock copolymer-based nanocomplexes encapsulating Que and siBCL2.
• Utilized biotin-mediated active targeting for enhanced cellular uptake and the "proton sponge effect" for cytosolic cargo release.
• Evaluated in vitro cytotoxicity and anti-metastasis activity, followed by in vivo studies in orthotopic 4T1 tumor-bearing mice.

Main Results:

• Que/siBCL2@BioMICs demonstrated enhanced cytotoxicity and anti-metastasis activity in vitro due to synergistic effects.
• In vivo studies showed superior anti-tumor efficacy, significantly reducing primary tumor burden and lung metastasis in mice.
• The nanocomplexes exhibited minimal side effects on major organs.

Conclusions:

• Biotin-targeted nanocomplexes effectively co-deliver quercetin and BCL-2 siRNA for synergistic cancer therapy.
• This strategy offers a promising approach for efficient treatment of triple-negative breast cancer (TNBC) by overcoming chemotherapy resistance.
• The developed nanocomplexes represent a viable platform for combined chemotherapeutic and nucleotide agent delivery.