Universität zu Köln

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. ORCID: 0000-0002-9870-0966, 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:	Creators Email ORCID ORCID Put Code Piaggio, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kondylis, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pastorino, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Paolo, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Perri, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cossu, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schorn, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marinaccio, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Murgia, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Daga, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Raggi, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Loi, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Emionite, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ognio, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, M. UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Ribatti, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ponzoni, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brignole, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEDIATED DEPLETION; NECROSIS-FACTOR; NEMO/IKK-GAMMA; CELL; PROGRESSION; APOPTOSIS; GROWTH; MODEL; NANOCARRIERS; INFLAMMATION Multiple languages Chemistry, Multidisciplinary; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28464