Coconut milk exosomal formulation of curcumin analog targets head and neck cancer progression through alterations in the HABP1signaling mechanism

Background: Head and neck cancer (HNC) is a malignancy characterized by uncontrolled cell growth with
increasing incidence rates and heterogeneity. Hyaluronan binding protein 1 (HABP1) is a glycoprotein that acts
as a cell surface marker, influencing the immune tumor environment, and is overexpressed in various epithelial
tumors. The role of HABP1 in HNC remains to be investigated. Exosome therapy has emerged as a promising
treatment that delivers anticancer compounds directly to tumor sites. Coconut milk is considered a valuable
therapeutic agent against cancer. Curcumin Analog Isoleucine (CAI) exhibits better solubility, improved antioxidant
properties, and greater antimutagenic effects than curcumin. In the study, we emphasized on exosomal
delivery of CAI to affect HABP1 signaling for effective cancer therapy.
Methods: The study focused on the isolation and characterization of tender coconut milk-derived exosomes.
Exosomal formulation was developed by loading tender coconut milk-derived exosomes with CAI (TC EXO+CAI)
through the sonication method. Bioaccessibility assessment was executed for the TC EXO+CAI along with the
MTT assay, morphology, nucleus shape, colony formation, AO-EtBr assays, western blot, and gene expression
analysis.
Results: The bioaccessibility of TC EXO+CAI was greater than that of CAI or curcumin. TC EXO+CAI was
cytotoxic to HNC cells at a lower IC50 value, indicating effective CAI delivery by exosomes. It causes cell
shrinkage, nuclear condensation, fewer colonies, and an increased number of apoptotic HNC cells. It reduced the
expression levels of HABP1 and associated molecules in HNC cells. The uptake of TC EXO+CAI by HNC cells
increases the expression of p53 and caspases, which effectively activates the apoptosis mechanism.
Conclusion: TC EXO+CAI exhibits target-specific delivery, which affects tumor cell physiology by reducing
HABP1 levels and prompting apoptosis in HNC cells.