A targeted liposomal delivery system for hydrophobic antitumor compounds using the example of a 1,2,3,4-tetrahydroisoquinoline derivative

Cancer is the second leading cause of death worldwide, after cardiovascular disorders. One of the main constraints of anticancer agents is their limited water solubility, which complicates preclinical in vivo studies. In this work, we propose a versatile approach for stabilizing hydrophobic antitumor agents using liposomes based on natural phospholipids. The efficacy of the method is demonstrated for hydrophobic 1-tridecyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, a promising tetrahydroisoquinoline derivative with proven antitumor activity against lymphoid and epithelial cancer cells. We show that the liposomal formulation ensures drug stability in aqueous media. Modification of the liposome surface with a HER2-specific non-immunoglobulin module strongly improved targeting efficiency. The targeting index differed markedly between cells with low versus high HER2 expression levels (3.02 and 18.98, respectively), demonstrating that the targeted liposomal formulation exerts a substantially enhanced cytotoxicity against HER2-overexpressing cells. The proposed liposomal platform can also be utilized to deliver other hydrophobic anticancer drugs.