Intravenous injection of hybrid liposomes suppresses the liver metastases in xenograft mouse models of colorectal cancer in vivo

Abstract

Therapeutic effects of hybrid liposomes (HL) composed of l-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(25) dodecyl ether (C(12)(EO)(25)) on the metastasis of human colon carcinoma (HCT116) cells were examined in vivo. Remarkably high therapeutic effects were obtained in the xenograft mouse models of colorectal cancer (CRC) liver metastases after treatment with HL-25 on the basis of relative liver weight and histological analysis of the liver tissue sections of mouse models with HE staining, and TUNEL staining for detection of apoptotic cells. The survival effects of HL-25 were obtained using xenograft mouse models of CRC liver metastases. Furthermore, with regard to pharmacokinetics, the accumulation of fluorescent labeled HL-25 was observed in the liver tissue of xenograft mouse models of CRC liver metastases for 24 h after the intravenous injection of fluorescent labeled HL-25. Therapeutic effects of HL without any drugs on the liver metastasis of human CRC were revealed for the first time in vivo.

Therapeutic Effects of Cationic Hybrid Liposomes on the Hepatic Metastasis of Colon Carcinoma Along with Apoptosis <i>in Vivo</i>

“…[17][18][19] Specific accumulation of HL including fluorescence probe into tumor cells that immunostained using carcinoembryonic antigen (CEA) as a histochemical marker of metastatic colon carcinoma in the liver of hepatic metastasis mouse models of colon carcinoma was observed using a confocal laser scanning microscope. 23) On the other hand, we elucidated the inhibitory effects on the growth of HCT116 cells along with apoptosis by cationic HL including electrically cationic lipid in vitro. 14) Enhanced expression of anionic lipids, phosphatidylserine (PS), in outer plasma membrane of the tumor cells as compared with in the normal cells has been reported.…”

Application of liposomes in drug development &ndash; focus on gastroenterological targets

“…[55][56][57] Intravenous administration of DMPC/ C 12 (EO) n or DMPC/docosahexaenoic acid hybrid liposomes into a liver metastases mouse model of xenografted human CRC exhibited significant therapeutic effects. [58][59][60] Hybrid liposomes preferentially accumulated into cancer cells and triggered cancer cell apoptosis which resulted in the inhibition of hepatic malignant transformation and prolonged survival of CRC mice with liver metastasis. At the same time, these hybrid liposomes did not show detectable toxicity in vivo.…”

Inhibitory Effects of Hybrid Liposomes on the Growth of Non-small Cell Lung Carcinoma Cells and Anti-invasive Activity by Ceramide Generation without any Drugs

“…The physical properties of HL such as shape, size, membrane fluidity of phase transition can be controlled by changing the constituents and compositional ratio. Remarkably high inhibitory effects of HL composed of DMPC and polyoxyethylene(n) dodecyl ethers (C 12 (EO) n ) on the growth of tumor cells in vitro [13][14][15][16][17], in vivo [17][18][19][20][21], and clinical application [22][23][24] have been obtained without drugs. We have reported HL induced apoptosis in various cancer cells including NSCLC (A549, H460, H23 and H520) cells [25].…”