Liposomal prednisolone inhibits tumor growth in a spontaneous mouse mammary carcinoma model.
J Control Release
; 243: 243-249, 2016 12 10.
Article
in En
| MEDLINE
| ID: mdl-27773734
ABSTRACT
Cancers are abundantly infiltrated by inflammatory cells that are modulated by tumor cells to secrete mediators fostering tumor cell survival and proliferation. Therefore, agents that interfere with inflammatory signaling molecules or specific immune cell populations have been investigated as anticancer drugs. Corticosteroids are highly potent anti-inflammatory drugs, whose activity is intensified when targeted by nanocarrier systems. Liposome-targeted corticosteroids have been shown to inhibit tumor growth in different syngeneic murine tumor models as well as human xenograft mouse models, which is attributed to a switch in the tumor microenvironment from a pro-inflammatory to an anti-inflammatory state. Despite the recognized value of implantation tumor models in preclinical research, the "acute" inflammation induced by inoculation of tumor cells together with the exponential tumor growth in a relatively short period of time does not resemble slow progressive human disease that develops in situ. Therefore, in this study, the antitumor effect of liposomal corticosteroids was investigated in a clinically more relevant setting of transgenic mice developing spontaneous breast carcinomas. Here we show that liposomal prednisolone phosphate inhibits the growth of spontaneous breast carcinoma. Interestingly, the liposomal prednisolone was significantly more active than free drug. At 72h after injection of the liposomal formulation, 3µg prednisolone per gram of tumor tissue was recovered whereas no drug could be recovered after injection of the free agent. This indicates that, despite etiological and morphological differences between implanted and spontaneous tumor models, EPR-mediated accumulation of drug occurs to similar extent in this spontaneous mammary carcinoma model as in the syngeneic tumor models. Finally, we analyzed miRNA profiles in the MMTV/neu model and showed that the top 10 of miRNAs in the MMTV/neu tumor consisted of miRNAs with a known involvement in breast carcinoma proliferation and metastasis. The only exception was the appearance of miR-146b, a known inflammation-regulating miRNA species, after liposomal prednisolone treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prednisolone
/
Antineoplastic Agents, Hormonal
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Glucocorticoids
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Mammary Neoplasms, Experimental
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2016
Document type:
Article
Affiliation country: