Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 14, Pages 12195-12202Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b15987
Keywords
self-assembly; colloids; protein corona; drug delivery; cell targeting
Funding
- U.S. National Institutes of General Medical Sciences [GM71630]
- Canadian Cancer Society Research Institute
- Natural Sciences and Engineering Research Council (NSERC) Postgraduate Research Scholarship
- NSERC postdoctoral fellowship
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While the formation of colloidal aggregates leads to artifacts in early drug discovery, their composition makes them attractive as nanoparticle formulations for targeted drug delivery as the entire nanoparticle is composed of drug. The typical transient stability of colloidal aggregates has inhibited exploiting this property. To overcome this limitation, we investigated a series of proteins to stabilize colloidal aggregates of the chemotherapeutic, fulvestrant, including the following: bovine serum albumin, a generic human immunoglobulin G, and trastuzumab, a therapeutic human epidermal growth factor receptor 2 antibody. Protein coronas reduced colloid size to <300 nm and improved their stability to over 48 h in both buffered saline and media containing serum protein. Unlike colloids stabilized with other proteins, trastuzumab-fulvestrant colloids were taken up by HER2 overexpressing cells and were cytotoxic. This new targeted formulation reimagines antibody-drug conjugates, delivering mM concentrations of drug to a cell.
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