Open AccessTuning Nanoparticle Interactions with Ovarian Cancer through Layer-by-Layer Modification of Surface Chemistry
Author(s) -
Santiago Correa,
Natalie Boehnke,
Antonio E. Barberio,
Elad DeissYehiely,
Aria Shi,
Benjamin Oberlton,
Sean G. Smith,
Ioannis K. Zervantonakis,
Erik C. Dreaden,
Paula T. Hammond
Publication year - 2020
Publication title -
acs nano
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.554
H-Index - 382
eISSN - 1936-086X
pISSN - 1936-0851
DOI - 10.1021/acsnano.9b09213
Subject(s) - polyelectrolyte , nanoparticle , surface charge , nanotechnology , biophysics , surface modification , layer by layer , materials science , nanocarriers , chemistry , layer (electronics) , biology , polymer , organic chemistry
Nanoparticle surface chemistry is a fundamental engineering parameter that governs tumor-targeting activity. Electrostatic assembly generates controlled polyelectrolyte complexes through the process of adsorption and charge overcompensation utilizing synthetic polyions and natural biomacromolecules; it can yield films with distinctive hydration, charge, and presentation of functional groups. Here, we used electrostatic layer-by-layer (LbL) assembly to screen 10 different surface chemistries for their ability to preferentially target human ovarian cancer in vitro . Our screen identified that poly-l-aspartate, poly-l-glutamate, and hyaluronate-coated LbL nanoparticles have striking specificity for ovarian cancer, while sulfated poly(β-cyclodextrin) nanoparticles target noncancerous stromal cells. We validated top candidates for tumor-homing ability with a murine model of metastatic disease and with patient-derived ovarian cancer spheroids. Nanoparticle surface chemistry also influenced subcellular trafficking, indicating strategies to target the cell membrane, caveolae, and perinuclear vesicles. Our results confirm LbL is a powerful tool to systematically engineer nanoparticles and achieve specific targeting.