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The vast majority of breast cancer mortality is due to metastatic disease. This stems from the fact that today’s drug delivery strategies treat metastasis as a monolith, while metastatic lesions display a highly heterogeneous cell population. Cancer cells continuously change the expression of targetable biomarkers over time and space, which results in different metastatic sites being targeted by different ligands. Thus, adapting conventional targeted drug delivery approaches is unlikely to work due to heterogeneity even across adjacent micrometastatic sites. To capture the dynamic nature of metastasis, we developed a dual-ligand nanoparticle by using two different types of ligands targeting EGFR and avß3 integrin. Animal studies showed that the dual-ligand nanoparticles were capable of targeting different metastatic sites within the same animal, which were otherwise missed. Importantly, the dual-ligand nanoparticle facilitated effective delivery of cytotoxic drugs, which yielded significant improvement in event-free survival in mouse models of breast cancer metastasis. |
