am6b15987_si_001.pdf (16.07 MB)
A New Spin on Antibody–Drug Conjugates: Trastuzumab-Fulvestrant Colloidal Drug Aggregates Target HER2-Positive Cells
journal contribution
posted on 2017-03-20, 00:00 authored by Ahil N. Ganesh, Christopher K. McLaughlin, Da Duan, Brian K. Shoichet, Molly S. ShoichetWhile
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.
History
Usage metrics
Categories
Keywords
trastuzumab-fulvestrant colloidsepidermal growth factor receptor 2 antibody48 hdrug discoveryHER 2 overexpressing cellsTrastuzumab-Fulvestrant Colloidal Drug Aggregates Target HER 2-Positive Cellsserum proteinimmunoglobulin Gnanoparticle formulationsaggregatecolloid sizestabilitydrug deliveryNew SpinmM concentrationsserum albuminProtein coronas
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC