Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer.
Jimena G DancyAniket S WadajkarNina P ConnollyRebeca GalisteoHeather M AmesSen PengNhan L TranOlga G GoloubevaGraeme F WoodworthJeffrey A WinklesAnthony J KimPublished in: Science advances (2020)
Development of effective tumor cell-targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed "DART" nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell-specific uptake. Here, we report that paclitaxel (PTX)-DART nanoparticles directed to the cell surface receptor fibroblast growth factor-inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain. These results provide new insights into methods for effective development of therapeutic nanoparticles as well as support the continued development of the DART platform for primary and metastatic tumors.
Keyphrases
- cell surface
- cancer therapy
- drug delivery
- small cell lung cancer
- squamous cell carcinoma
- metastatic breast cancer
- single cell
- cell therapy
- binding protein
- coronary artery
- mesenchymal stem cells
- computed tomography
- mass spectrometry
- high throughput
- brain injury
- drug release
- blood brain barrier
- cerebral ischemia
- dna binding
- optic nerve