Merging fusogenic DOPE and a tumour targeted self-assembling biopolymer: Smart hybrid liposomes for drug vectorization in cancer therapy

In this study, a smart hybrid liposome system was achieved combining a self-assembling biopolymer conjugate (human serum albumin-hyaluronic acid) with targeting and redox-responsive activity with dioleoyl phosphatidylethanolamine, a fusogenic phospholipid. The obtained hybrid liposomal structures were found to possess suitable physicochemical properties for cancer therapy application, with mean size of 65 nm, negative surface charge (-27 mV) and the ability to efficiently encapsulate Doxorubicin in the inner liposomal core with high efficiency. The drug loaded hybrid liposomes (DOX@HBLs) were able to trigger the drug release under simulated acidic and redox conditions of the tumor environment, whereas the biological characterization demonstrated the safety and the selectivity of the formulation, able to target the cancer cells (toxicity similar to that of the free drug) while sparing the healthy cells (viability > 90 % in all cases). Furthermore, compared to free drug, DOX@HBLs were able to reduce cell motility, impair metabolic pathways essential for cancer progression, and effectively inhibit spheroid formation (by almost 50 % after 20 days incubation) in both Estrogen Receptor-positive and Triple Negative Breast Cancer cells, demonstrating their high potential as unconventional drug delivery vectors in cancer therapy.