PT  - JOURNAL ARTICLE
AU  - Natalie Boehnke
AU  - Joelle P. Straehla
AU  - Hannah C. Safford
AU  - Mustafa Kocak
AU  - Matthew G. Rees
AU  - Melissa Ronan
AU  - Charles H. Adelmann
AU  - Raghu R. Chivukula
AU  - Jaime H. Cheah
AU  - Hojun Li
AU  - David M. Sabatini
AU  - Jennifer A. Roth
AU  - Angela N. Koehler
AU  - Paula T. Hammond
TI  - Massively parallel pooled screening reveals genomic determinants of nanoparticle-cell interactions
AID  - 10.1101/2021.04.05.438521
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.05.438521
4099  - http://biorxiv.org/content/early/2021/04/06/2021.04.05.438521.short
4100  - http://biorxiv.org/content/early/2021/04/06/2021.04.05.438521.full
AB  - To accelerate the translation of cancer nanomedicine, we hypothesize that integrated genomic screens will improve understanding of the cellular processes governing nanoparticle trafficking. We developed a massively parallel high-throughput screening method leveraging barcoded, pooled cancer cell lines annotated with multi-omic data to investigate cell association patterns across a nanoparticle library spanning a range of formulations with clinical potential. This approach identified both the materials properties and cell-intrinsic features mediating nanoparticle-cell association. Coupling the data with machine learning algorithms, we constructed genomic nanoparticle trafficking networks and identified nanoparticle-specific biomarkers. We engineered cell lines to validate SLC46A3 as a biomarker whose expression inversely predicts liposomal nanoparticle uptake. Our work establishes the power of massively parallel pooled cell screens and enables the identification and utilization of nanoparticle predictive biomarkers to rationally design nanoformulations for specific patient populations.Competing Interest StatementThe authors have declared no competing interest.