Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery.

Autor: Boehnke N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Straehla JP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA., Safford HC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Kocak M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Rees MG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Ronan M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Rosenberg D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Adelmann CH; Cutaneous Biology Research Center, Massachusetts General Hospital Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Chivukula RR; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Nabar N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Berger AG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Lamson NG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Cheah JH; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Li H; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA., Roth JA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Koehler AN; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Hammond PT; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Jul 22; Vol. 377 (6604), pp. eabm5551. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1126/science.abm5551
Abstrakt: 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.
Databáze: MEDLINE
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