Targeted delivery of therapeutics to metastatic lung cancer cells using aptamer-conjugated nanoemulsions

Abstract

Lung cancer is the primary cause of cancer-related deaths, with a five-year overall survival rate of 15 %, mainly related to late diagnosis at advanced stages. Despite recent improvements in cancer medicine, metastatic disease still, in fact, represents the main challenge for effective therapies. Targeting disseminated cells requires a better understanding of the underlying biological mechanisms and a paradigm shift to devise innovative treatments.

Nanomedicine could open up new perspectives in cancer management, as nanoparticles offer many advantages in drug delivery due to their intrinsic properties, such as better bioavailability and the potential for selective targeting. A strategy to enhance delivery at the site of action is to use nanomedicines targeting specific receptors overexpressed in cancer cells or the tumor microenvironment. We recently identified TAS1R3 as an ideal target, enriched in metastatic lung cancer cells and highly expressed in the CD133+ cancer stem cell (CSC) subset.

We developed and evaluated a targeted formulation of sphingomyelin nanoemulsions functionalized with a TAS1R3-specific aptamer (SN-5F). SN-5F exhibited high stability in both aqueous media and biofluids and was efficiently internalized by cell models overexpressing the targeted receptor, including the usually hard-to-target CD133+ CSC population. SN-5F was evaluated in 2D and 3D cell cultures, as well as in vivo using patient-derived xenografts, where it successfully reached disseminated cancer cells and delivered hydrophobic drugs to CSCs, resulting in reduced tumor-forming potential.

These results highlight the promise of rationally designed, receptor-targeted nanomedicines as a novel approach for anti-metastatic lung cancer therapy.