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Penetration and uptake of Nanoparticles in 3D tumour spheroids

Tchoryk, Aleksandra; Taresco, Vincenzo; Argent, Richard; Ashford, Marianne B.; Gellert, Paul; Stolnik, Snow; Grabowska, Anna M.; Garnett, Martin C.

Authors

Aleksandra Tchoryk

Vincenzo Taresco

Richard Argent

Marianne B. Ashford

Paul Gellert

Snow Stolnik

Anna M. Grabowska

Martin C. Garnett



Abstract

Animal models are effective for assessing tumour localisation of nanosystems, but difficult to use for studying penetration beyond the vasculature. Here, we have used well-characterised HCT116 colorectal cancer spheroids to study the effect of nanoparticle (NP) physicochemical properties on penetration and uptake. Incubation of spheroids with Hoechst 33342 resulted in a dye gradient which facilitated discrimination between the populations of cells in the core and at the periphery of spheroids by flow cytometry. This approach was used to compare doxorubicin and liposomal doxorubicin (Caelyx®), and a range of model poly(styrene) nanoparticles of different sizes (30 nm, 50 nm, 100 nm) and with different surface chemistries (50 nm uniform plain, carboxylated, aminated and a range of NPs and polyethylene glycol modified NPs prepared from a promising new functionalized biodegradable polymer (poly(glycerol-adipate), PGA). Unmodified poly(styrene) nanoparticles (30 nm/50 nm) were able to penetrate to the core of HCT116 spheroids more efficiently than larger poly(styrene) nanoparticles (100 nm). Surprisingly, penetration of 30 and 50nm particles was as good as clinically relevant doxorubicin concentrations. However penetration was reduced with higher surface charge. PGA NPs of 100 nm showed similar penetration into spheroids as 50 nm poly(styrene) nanoparticles, which may be related to polymer flexibility. PEG surface modification of polymeric particles significantly improved penetration into the spheroid core. The new model combining the use of spheroids Hoechst staining and flow cytometry was a useful model for assessing NP penetration and gives useful insights into the effects of NPs physical properties when designing nanomedicines.

Journal Article Type Article
Publication Date Apr 4, 2019
Journal Bioconjugate Chemistry
Print ISSN 1043-1802
Electronic ISSN 1520-4812
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 30
Issue 5
Pages 1371-1384
APA6 Citation Tchoryk, A., Taresco, V., Argent, R., Ashford, M. B., Gellert, P., Stolnik, S., …Garnett, M. C. (2019). Penetration and uptake of Nanoparticles in 3D tumour spheroids. Bioconjugate Chemistry, 30(5), 1371-1384. https://doi.org/10.1021/acs.bioconjchem.9b00136
DOI https://doi.org/10.1021/acs.bioconjchem.9b00136
Keywords Biotechnology; Organic Chemistry; Bioengineering; Pharmacology; Pharmaceutical Science; Biomedical Engineering
Publisher URL https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00136

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