Multifunctional TK-VLPs nanocarrier for tumor-targeted delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Virus-like particles (VLPs) are versatile platforms for biomedical applications, including disease diagnosis, prevention, and therapy.
• Targeted drug delivery systems are crucial for improving therapeutic efficacy and reducing side effects in cancer treatment.

Purpose of the Study:

• To develop and characterize a novel multifunctional VLP nanocarrier (TK-VLPs) for tumor-targeted delivery.
• To evaluate the targeting capabilities of TK-VLPs to specific cancer cells and tumor vasculature.
• To assess the potential of TK-VLPs as a drug delivery system for colorectal cancer.

Main Methods:

• Preparation and characterization of TK-VLPs using the baculovirus expression system.
• Surface Plasmon Resonance (SPR) and cell uptake assays to determine ligand-receptor interactions.
• Confocal laser scanning microscopy and flow cytometry for cellular targeting validation.
• In vivo studies in mice to assess tumor targeting and drug delivery efficiency.
• Cytotoxicity assays to evaluate the selectivity of TK-VLPs-DOX for colorectal cancer cells.

Main Results:

• The TK peptide demonstrated bi-functional ligand activity, binding to Caco-2, HRT-18, and HUVEC cells via integrin α6β1 and αvβ3 receptors.
• Successful preparation of TK-VLPs confirmed by immunofluorescence, SDS-PAGE, and western blot.
• TK-VLPs showed specific targeting to Caco-2, HRT-18, and HUVEC cells in vitro.
• In vivo studies confirmed TK-VLPs targeted tumor cells and vasculature in mice, delivering fluorescein efficiently.
• TK-VLPs-DOX exhibited enhanced selectivity for colorectal cancer cells, with a uniform spherical shape and ~28nm size.

Conclusions:

• TK-VLPs are successfully prepared multifunctional nanocarriers with demonstrated targeting capabilities for colon tumor cells and tumor angiogenesis.
• The enhanced permeability and retention (EPR) effect contributes to the efficacy of TK-VLPs in targeting tumor sites.
• TK-VLPs hold significant potential as a nanocarrier for targeted drug delivery systems in colorectal cancer therapy.