Hyaluronic-Acid-Tagged Cubosomes Deliver Cytotoxics Specifically to CD44-Positive Cancer Cells

Area of Science:

• Nanotechnology
• Drug Delivery
• Cancer Therapeutics

Background:

• Chemotherapy drug delivery aims to increase tumor drug concentration and reduce systemic toxicity.
• Cubosomes offer biocompatibility and high drug loading for chemotherapy.
• Active targeting of cubosomes to cancer cells is an underexplored area.

Purpose of the Study:

• To formulate and characterize hyaluronic acid (HA)-tagged cubosomes loaded with copper acetylacetonate for targeted cancer therapy.
• To evaluate the efficacy of HA-tagged cubosomes in targeting CD44-expressing cancer cells.

Main Methods:

• Cubosomes loaded with copper acetylacetonate were formulated and surface-functionalized with HA via click chemistry.
• Characterization included hydrodynamic diameter and internal nanostructure (Im3m space group).
• Cellular uptake and cytotoxicity assays were performed on CD44-positive and CD44-negative cancer cell lines (MDA-MB-231, HT29, MCF-7, HEK-293).

Main Results:

• HA-tagged cubosomes exhibited an average hydrodynamic diameter of 152 nm.
• Efficient uptake was observed in CD44-positive cancer cells (MDA-MB-231, HT29), but not in CD44-negative cells (MCF-7, HEK-293).
• HA-tagged cubosomes induced significantly greater apoptotic cell death in CD44-positive cells compared to untargeted cubosomes, demonstrating specific targeting.

Conclusions:

• HA-tagged, copper acetylacetonate-loaded cubosomes show potential for selective targeting of CD44-expressing tumors.
• This targeted approach enhances therapeutic efficacy and reduces off-target effects.
• The findings support the development of cubosomes as a promising platform for precision cancer therapy.