Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.
Int J Pharm
; 566: 541-548, 2019 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-31173801
ABSTRACT
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-co-glycolic acid) (PLGA) NPs (155⯱â¯10â¯nm) were delivered via the ileocolic vein to metastatic livers 15â¯min after localized MW irradiation (1â¯min, 41⯰C) or in normothermia (37⯰C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1â¯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.
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Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Hepatócitos
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Nanopartículas
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Copolímero de Ácido Poliláctico e Ácido Poliglicólico
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Hipertermia Induzida
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article