Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model

Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model. Liu, L. Y., Ma, X., Ouyang, B., Ings, D. P., Marwah, S., Liu, J., Chen, A. Y., Gupta, R., Manuel, J., Chen, X., Gage, B. K., Cirlan, I., Khuu, N., Chung, S., Camat, D., Cheng, M., Sekhon, M., Zagorovsky, K., Abdou Mohamed, M. A., Thoeni, C., Atif, J., Echeverri, J., Kollmann, D., Fischer, S., Bader, G. D., Chan, W. C. W., Michalak, T. I., McGilvray, I. D., & MacParland, S. A. ACS Nano, 14(4):4698–4715, April, 2020. Publisher: American Chemical Society

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Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model [pdf]

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There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. However, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. We introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Liver cancer development in these out-bred animals occurs as a result of persistent viral infection, mimicking human hepatitis B virus-induced HCC development. We highlight how this model addresses key gaps associated with other commonly used tumor models. We employed this model to (1) track organ biodistribution of gold NPs after intravenous administration, (2) examine their subcellular localization in the liver, (3) determine clearance kinetics, and (4) characterize the identity of hepatic macrophages that take up NPs using RNA-sequencing (RNA-seq). We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed accumulation of NPs in the lysosomes of CD14+ cells. Through RNA-seq, we uncovered that immunosuppressive macrophages within the woodchuck liver are the major cell type that take up injected NPs. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.

@article{liu_nanoparticle_2020,
	title = {Nanoparticle {Uptake} in a {Spontaneous} and {Immunocompetent} {Woodchuck} {Liver} {Cancer} {Model}},
	volume = {14},
	issn = {1936-0851},
	url = {https://doi.org/10.1021/acsnano.0c00468},
	doi = {10.1021/acsnano.0c00468},
	abstract = {There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. However, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. We introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Liver cancer development in these out-bred animals occurs as a result of persistent viral infection, mimicking human hepatitis B virus-induced HCC development. We highlight how this model addresses key gaps associated with other commonly used tumor models. We employed this model to (1) track organ biodistribution of gold NPs after intravenous administration, (2) examine their subcellular localization in the liver, (3) determine clearance kinetics, and (4) characterize the identity of hepatic macrophages that take up NPs using RNA-sequencing (RNA-seq). We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed accumulation of NPs in the lysosomes of CD14+ cells. Through RNA-seq, we uncovered that immunosuppressive macrophages within the woodchuck liver are the major cell type that take up injected NPs. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.},
	number = {4},
	urldate = {2021-11-06},
	journal = {ACS Nano},
	author = {Liu, Lewis Y. and Ma, Xue-Zhong and Ouyang, Ben and Ings, Danielle P. and Marwah, Sagar and Liu, Jeff and Chen, Annie Y. and Gupta, Rahul and Manuel, Justin and Chen, Xu-Chun and Gage, Blair K. and Cirlan, Iulia and Khuu, Nicholas and Chung, Sai and Camat, Damra and Cheng, Michael and Sekhon, Manmeet and Zagorovsky, Kyryl and Abdou Mohamed, Mohamed A. and Thoeni, Cornelia and Atif, Jawairia and Echeverri, Juan and Kollmann, Dagmar and Fischer, Sandra and Bader, Gary D. and Chan, Warren C. W. and Michalak, Tomasz I. and McGilvray, Ian D. and MacParland, Sonya A.},
	month = apr,
	year = {2020},
	note = {Publisher: American Chemical Society},
	pages = {4698--4715},
	file = {Full Text PDF:files/1814/Liu et al. - 2020 - Nanoparticle Uptake in a Spontaneous and Immunocom.pdf:application/pdf;ACS Full Text Snapshot:files/1819/acsnano.html:text/html},
	url_Paper = {https://inbs.med.utoronto.ca/wp-content/uploads/2020/08/acsnano.0c00468-min.pdf}
}

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