Multiwalled Carbon Nanotubes for Combination Therapy: a Biodistribution and Efficacy Pilot Study

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Multiwalled carbon nanotubes offer potential for drug delivery systems.
• Combined therapeutic approaches are crucial for aggressive cancers like triple-negative breast cancer.
• Targeted drug delivery and imaging capabilities can enhance therapeutic efficacy.

Purpose of the Study:

• To develop and characterize a novel drug delivery system (DDS) based on oxidized multiwalled carbon nanotubes.
• To load the DDS with doxorubicin, metformin, a biotin targeting agent, and a radiolabeling tag for imaging.
• To evaluate the DDS biodistribution, efficacy, and toxicity in a preclinical model of triple-negative breast cancer.

Main Methods:

• Synthesis of a drug delivery system using short oxidized multiwalled carbon nanotubes.
• Loading of doxorubicin, metformin, biotin, and a radiolabeling tag (Ga-68 or Cu-64).
• Biodistribution studies using Positron Emission Tomography/Computed Tomography (PET/CT) in 4T1 tumor-bearing mice.
• Evaluation of therapeutic efficacy and survival rates in the animal model.

Main Results:

• The DDS successfully encapsulated doxorubicin, metformin, biotin, and a radiolabeling tag.
• Biodistribution profiles varied depending on administration methods.
• A marginal survival benefit was observed in 20% of mice with triple-negative breast cancer, extending survival by approximately 1.5 weeks.
• The DDS exhibited good tolerability, with no observed toxicity concerns related to carbon nanotubes.

Conclusions:

• The developed carbon nanotube-based DDS is a promising platform for combined chemo-immunotherapy and theranostics.
• The system demonstrates potential for treating aggressive triple-negative breast cancer models.
• Further research is warranted to optimize the DDS for enhanced therapeutic outcomes and clinical translation.