Tumor penetration of Sub-10 nm nanoparticles: effect of dendrimer properties on their penetration in multicellular tumor spheroids

J. Bugno, Michael J. Poellmann, K. Sokolowski, Hao jui Hsu, Dong Hwan Kim, Seungpyo Hong

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Ultrasmall nanoparticles (NPs, <10 nm) have promise in cancer treatment, yet little is known about how NP physical properties influence penetration through solid tumors. To elucidate the role of NP size and structure, we prepared a series of sub-10 nm poly(amidoamine) (PAMAM) dendrimers and gold NPs (AuNP), and evaluated penetration in multicellular tumor spheroids (MCTS). Smaller generation 2 dendrimers (G2-NH2, 2.9 nm diameter) penetrated 2.5-fold deeper than larger G7-NH2 (8.1 nm) (P = 0.0005). Despite increased accumulation within MCTS, electrostatic cell interactions and ligand (folic acid, FA)-mediated targeting had minimal influence on penetration. NP rigidity played a minor role in penetration, with smaller rigid AuNP (2 nm) penetrating significantly more than larger AuNP (4 nm) (3-fold, P = 0.014; G2-NH2 vs. G4-NH2, 2.8-fold, P = 0.033). Our findings highlight the importance of rational NP design and provide design cues for tailored NP distributions within solid tumors.

Original languageEnglish
Article number102059
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume21
DOIs
Publication statusPublished - 2019 Oct

Bibliographical note

Funding Information:
This study was supported by the National Science Foundation (NSF) under grant # DMR-1409161/1741560/1808251. The research was partially conducted in a facility constructed with support from the NIH (grant C06RR15482). J.B. received support in the form of fellowships from the American Association of Pharmaceutical Scientists (AAPS) and the American Foundation for Pharmaceutical Education (AFPE).? Acknowledgement This study was supported by the National Science Foundation (NSF) under grant # DMR-1409161/1741560/1808251. The research was partially conducted in a facility constructed with support from the NIH (grant C06RR15482). J.B. received support in the form of fellowships from the American Association of Pharmaceutical Scientists (AAPS) and the American Foundation for Pharmaceutical Education (AFPE).

Publisher Copyright:
© 2019 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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