Tuning Nanoparticle Interactions with Ovarian Cancer through Layer-by-Layer Modification of Surface Chemistry

Santiago Correa, Natalie Boehnke, Antonio E. Barberio, Elad Deiss-Yehiely, Aria Shi, Benjamin Oberlton, Sean G. Smith, Ioannis Zervantonakis, Erik C. Dreaden, Paula T. Hammond

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2224-2237
Number of pages14
JournalACS nano
Issue number2
StatePublished - Feb 25 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.


  • layer-by-layer
  • nanomedicine
  • nanoparticles
  • ovarian cancer
  • subcellular targeting
  • surface chemistry
  • tumor-targeting


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