Decreased Nonspecific Adhesivity, Receptor-targeted Therapeutic Nanoparticles for Primary and Metastatic Breast Cancer

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Jan 31

PMID 31998833

Citations 32

Authors

Jimena G Dancy

Aniket S Wadajkar

Nina P Connolly

Rebeca Galisteo

Heather M Ames

Sen Peng

Nhan L Tran

Olga G Goloubeva

Graeme F Woodworth

Jeffrey A Winkles

Anthony J Kim

Affiliations

Soon will be listed here.

Abstract

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.

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