Piaggio, F., Kondylis, V., Pastorino, F., Di Paolo, D., Perri, P., Cossu, I., Schorn, F., Marinaccio, C., Murgia, D., Daga, A., Raggi, F., Loi, M., Emionite, L., Ognio, E., Pasparakis, M., Ribatti, D., Ponzoni, M. and Brignole, C. (2016). A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma: Anti-angiogenic and anti-tumor effects. J. Control. Release, 223. S. 165 - 178. AMSTERDAM: ELSEVIER. ISSN 1873-4995

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Abstract

The depletion of tumor-associated macrophages (TAMs), involved in different stages of cancer development and progression, is an appealing strategy in cancer therapy. We developed novel Clodronate-containing liposomes (Clo-Lipo-DOTAP) presenting physicochemical properties (size distribution, polydispersity index and Z-potential) suited for safe storage and injections. In vitro, Clo-Lipo-DOTAP inhibited proliferation, reduced viability and induced apoptosis of a macrophage-like cell line in a dose- and time-dependent manner. In proof of functionality experiments, Clo-Lipo-DOTAP depleted macrophages in a genetic mouse model of chronic hepatitis and hepatocellular carcinoma leading to a significant reduction of F4/80-positive cells in the liver and spleen of treated mice compared to PBS-treated controls. The number of granulocytes, B and T lymphocytes was not affected. In B16/F10 subcutaneous melanoma-bearingmice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P < 0.001). Within the tumors, the expression F4/80 and alpha-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-alpha, VEGF and PDGF-bb were statistically decreased. In B16/F10 lung metastatic melanoma model, treatment with Clo-Lipo-DOTAP significantly reduced the number of pulmonary nodules (P < 0.05). F4/80-positive cells and microvessel density were statistically decreased. In conclusion, the depletion of TAMs in primary and metastatic melanoma presents anti-tumor efficacy via inhibition of angiogenesis and modulation of inflammation related cytokines. (C) 2015 Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Piaggio, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kondylis, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pastorino, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Paolo, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perri, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cossu, I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schorn, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marinaccio, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murgia, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daga, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raggi, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loi, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Emionite, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ognio, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ribatti, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ponzoni, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brignole, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-284646
DOI: 10.1016/j.jconrel.2015.12.037
Journal or Publication Title: J. Control. Release
Volume: 223
Page Range: S. 165 - 178
Date: 2016
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1873-4995
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MEDIATED DEPLETION; NECROSIS-FACTOR; NEMO/IKK-GAMMA; CELL; PROGRESSION; APOPTOSIS; GROWTH; MODEL; NANOCARRIERS; INFLAMMATIONMultiple languages
Chemistry, Multidisciplinary; Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28464

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