Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery

Science. 2022 Jul 22;377(6604):eabm5551. doi: 10.1126/science.abm5551. Epub 2022 Jul 22.


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.

MeSH terms

  • Animals
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / metabolism
  • Biomarkers, Pharmacological*
  • Cell Line, Tumor
  • Copper Transport Proteins* / genetics
  • Drug Compounding*
  • Gene Expression
  • Genomics
  • Humans
  • Liposomes
  • Mice
  • Nanomedicine
  • Nanoparticle Drug Delivery System*
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism


  • Antineoplastic Agents
  • Biomarkers, Pharmacological
  • Copper Transport Proteins
  • Liposomes
  • Nanoparticle Drug Delivery System