Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer
PublisherAmerican Association for the Advancement of Science
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AbstractDevelopment 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. Copyright 2020 The Authors
SponsorsThis research was supported in part by the National Institutes of Health [R37 CA218617 (A.J.K.) and R01 NS107813 (G.F.W.)] and an Institutional Research Grant IRG-97-153-10 (A.S.W.) from the American Cancer Society. J.G.D., A.S.W., and N.P.C. were supported in part by NIH Training Grant T32 CA154274. J.G.D. was also supported by an NIGMS Initiative for Maximizing Student Development Grant (R25 GM55036).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85078176625&doi=10.1126%2fsciadv.aax3931&partnerID=40&md5=6bebae3ebb86100ca3993a7f905f508a; http://hdl.handle.net/10713/11659