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

doi:10.1016/j.nano.2019.102059

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

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

27 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 language	English
Article number	102059
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	21
DOIs	https://doi.org/10.1016/j.nano.2019.102059
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.nano.2019.102059

Cite this

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

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.",

author = "J. Bugno and Poellmann, {Michael J.} and K. Sokolowski and Hsu, {Hao jui} and Kim, {Dong Hwan} and Seungpyo Hong",

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: {\textcopyright} 2019 Elsevier Inc.",

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N1 - 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.

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N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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