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      1. Author :
        Piaggio, F; Kondylis, V; Pastorino, F; Di Paolo, D; Perri, P; Cossu, I; Schorn, F; Marinaccio, C; Murgia, D; Daga, A
      2. Title :
        A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma: Anti-angiogenic and anti-tumor effects
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        Journal of Controlled Release
      6. Products :
      7. Volume :
      8. Issue :
      9. Page Numbers :
      10. Research Area :
      11. Keywords :
        TAMs;; Liposomal Clodronate;; Adjuvant therapy;; Melanoma; IVIS; IVIS BLI in vivo
      12. 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-bearing mice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P < 0.001). Within the tumors, the expression F4/80 and α-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-α, 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.
      13. URL :
      14. Call Number :
        PKI @ user @ 10597
      15. Serial :