Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs

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TitreTumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs
Type de publicationJournal Article
Year of Publication2019
AuteursCastellani C, Fedrigo M, Tavano R, Cappellini R, Fedeli C, Mognato M, Abdel-Mottaleb MMA, Lamprecht A, Tudorancea I, Porumb V, Iliescu R, Angelini A, Papini E, Dimofte G
JournalINTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume566
Pagination541-548
Date PublishedJUL 20
Type of ArticleArticle
ISSN0378-5173
Mots-clésHepatocytes, Liver cancer metastasis, Mild hyperthermia, PLGA-NPs, Tumor associated macrophages
Résumé

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-coglycolic acid) (PLGA) NPs (155 +/- 10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 degrees C) or in normothermia (37 degrees C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

DOI10.1016/j.ijpharm.2019.06.004