Abstract
The depletion of tumor-associated macrophages (TAMs), involved in different stages of cancer development and progression, is an appealing strategy in cancer therapy. Wedeveloped 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-bearing mice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P <0.001). Within the tumors, the expression F4/80 and a-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-a, 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 b 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.
| Original language | English |
|---|---|
| Pages (from-to) | 165-177 |
| Number of pages | 13 |
| Journal | Journal of Controlled Release |
| Volume | 223 |
| DOIs | |
| Publication status | Published - Feb 10 2016 |
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Keywords
- Adjuvant therapy
- Liposomal Clodronate
- Melanoma
- TAMs
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma : Anti-angiogenic and anti-tumor effects. / Piaggio, Francesca; Kondylis, V.; Pastorino, Fabio; Di Paolo, Daniela; Perri, Patrizia; Cossu, Irene; Schorn, F.; Marinaccio, Christian; Murgia, Daniele; Daga, Antonio; Raggi, Federica; Loi, Monica; Emionite, Laura; Ognio, Emanuela; Pasparakis, M.; Ribatti, Domenico; Ponzoni, Mirco; Brignole, Chiara.
In: Journal of Controlled Release, Vol. 223, 10.02.2016, p. 165-177.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma
T2 - Anti-angiogenic and anti-tumor effects
AU - Piaggio, Francesca
AU - Kondylis, V.
AU - Pastorino, Fabio
AU - Di Paolo, Daniela
AU - Perri, Patrizia
AU - Cossu, Irene
AU - Schorn, F.
AU - Marinaccio, Christian
AU - Murgia, Daniele
AU - Daga, Antonio
AU - Raggi, Federica
AU - Loi, Monica
AU - Emionite, Laura
AU - Ognio, Emanuela
AU - Pasparakis, M.
AU - Ribatti, Domenico
AU - Ponzoni, Mirco
AU - Brignole, Chiara
PY - 2016/2/10
Y1 - 2016/2/10
N2 - The depletion of tumor-associated macrophages (TAMs), involved in different stages of cancer development and progression, is an appealing strategy in cancer therapy. Wedeveloped 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-bearing mice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P <0.001). Within the tumors, the expression F4/80 and a-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-a, 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 b 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.
AB - The depletion of tumor-associated macrophages (TAMs), involved in different stages of cancer development and progression, is an appealing strategy in cancer therapy. Wedeveloped 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-bearing mice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P <0.001). Within the tumors, the expression F4/80 and a-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-a, 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 b 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.
KW - Adjuvant therapy
KW - Liposomal Clodronate
KW - Melanoma
KW - TAMs
UR - http://www.scopus.com/inward/record.url?scp=84953208681&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84953208681&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.12.037
DO - 10.1016/j.jconrel.2015.12.037
M3 - Article
VL - 223
SP - 165
EP - 177
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -