Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer
Menée in vitro et à l'aide d'un modèle murin de cancer du sein triple négatif et d'un modèle de tumeur intracrânienne ayant pour origine un cancer du sein triple négatif, cette étude analyse l'efficacité thérapeutique de nanoparticules chargées en paclitaxel, ciblant le récepteur de surface Fn14 et interagissant faiblement avec les composants du sang et des tissus tumoraux
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.
Science Advances 2020