Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 21, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2019.102059
Keywords
Nanoparticles; Dendrimer; Cancer; Tumor; Penetration
Funding
- National Science Foundation (NSF) [DMR-1409161/1741560/1808251]
- NIH [C06RR15482]
- American Association of Pharmaceutical Scientists (AAPS)
- American Foundation for Pharmaceutical Education (AFPE)
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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. (C) 2019 Elsevier Inc. All rights reserved.
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