Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery.
Science
; 377(6604): eabm5551, 2022 07 22.
Article
em En
| MEDLINE
| ID: mdl-35862544
ABSTRACT
To accelerate the translation of cancer nanomedicine, we used an integrated genomic approach to improve our understanding of the cellular processes that govern nanoparticle trafficking. We developed a massively parallel screen that leverages barcoded, pooled cancer cell lines annotated with multiomic data to investigate cell association patterns across a nanoparticle library spanning a range of formulations with clinical potential. We identified both materials properties and cell-intrinsic features that mediate nanoparticle-cell association. Using machine learning algorithms, we constructed genomic nanoparticle trafficking networks and identified nanoparticle-specific biomarkers. We validated one such biomarker gene expression of SLC46A3, which inversely predicts lipid-based nanoparticle uptake in vitro and in vivo. Our work establishes the power of integrated screens for nanoparticle delivery and enables the identification and utilization of biomarkers to rationally design nanoformulations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Composição de Medicamentos
/
Nanopartículas
/
Biomarcadores Farmacológicos
/
Proteínas de Transporte de Cobre
/
Sistemas de Liberação de Fármacos por Nanopartículas
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos