1. Tumor penetration of Sub-10 nm nanoparticles: effect of dendrimer properties on their penetration in multicellular tumor spheroids.
- Author
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Bugno J, Poellmann MJ, Sokolowski K, Hsu HJ, Kim DH, and Hong S
- Subjects
- Humans, MCF-7 Cells, Dendrimers chemistry, Dendrimers pharmacokinetics, Dendrimers pharmacology, Drug Delivery Systems, Gold chemistry, Gold pharmacokinetics, Gold pharmacology, Metal Nanoparticles chemistry, Metal Nanoparticles therapeutic use, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms pathology, Spheroids, Cellular metabolism, Spheroids, Cellular pathology
- 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-NH
2 , 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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