Enhanced gene transfection in macrophages by histidine-conjugated mannosylated cationic liposomes.

Targeted gene delivery to macrophages is important for the treatments of various immune diseases. Since macrophages express mannose receptors, development of efficient mannosylated non-viral carriers is an effective approach to macrophages-selective in vivo gene transfection. In this study, a pH-sensitive mannosylated cholesterol derivative, Man-His-C4-Chol, which possesses histidine (His) residues, containing lipoplexes (Man-His-lipoplexes) was characterized for transfection both in vitro and in vivo.

Mannosylated cationic liposomes/CpG DNA complex for the treatment of hepatic metastasis after intravenous administration in mice.

Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory hepatic metastasis. In this study, we report the use of a conventional cationic liposomes/CpG DNA complex (Bare/CpG DNA lipoplex) and a mannosylated cationic liposomes/CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of hepatic metastasis in mice. After intravenous administration of Bare/CpG DNA lipoplex, higher amounts of IL-12 and IFN-gamma were produced in serum or liver compared with naked CpG DNA, and their production was increased further by Man/CpG DNA lipoplex.

Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG DNA/cationic liposome complex in mice.

Peritoneal dissemination remains the most difficult type of metastasis to treat, and current systemic chemotherapy or radiotherapy tends to have little effect; therefore, immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach. Recently, we have reported that intraperitoneal administration of phosphodiester (PO) CpG DNA-lipoplex could efficiently inhibit peritoneal dissemination in mice. In this study, chemically modified phosphorothioate (PS)-CpG DNA and natural PO-CpG DNA were complexed with DOTMA/cholesterol cationic liposomes (PS-CpG DNA-lipoplex and PO-CpG DNA-lipoplex) and their antitumor activity was evaluated in a mouse model of peritoneal dissemination.

Use of mannosylated cationic liposomes/ immunostimulatory CpG DNA complex for effective inhibition of peritoneal dissemination in mice.

Background: Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory peritoneal dissemination. In the present study, we report the use of a mannosylated cationic liposomes/immunostimulatory CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of peritoneal dissemination in mice.

Methods: The immune response characteristics of the Man/CpG DNA lipoplex were evaluated by measuring tumor necrosis factor (TNF)-alpha production using primary cultured mouse peritoneal macrophages.

[Immunotherapy against peritoneal dissemination by immunostimulatory CpG DNA].

Peritoneal dissemination is one of the most common causes of metastasis from malignancies in the abdominal cavity. However, the treatment of peritoneal dissemination is difficult; patients receiving normal chemotherapy have a 0-1% chance of surviving for 5 years. Milky spots in the greater omentum are considered to facilitate the adhesion and invasion of abdominal free cancer cells, and subsequently lymph node metastasis occurs.

Inhibition of peritoneal dissemination of tumor cells by cationized catalase in mice.

To inhibit peritoneal dissemination of tumor cells by destroying hydrogen peroxide, ethylenediamine-conjugated catalase (ED-catalase), a cationized derivative, was injected into the peritoneal cavity of mice. ED-catalase had about a 6-fold longer retention time within the cavity than unmodified catalase. Peritoneal dissemination was evaluated after intraperitoneal inoculation of B16-BL6/Luc, a melanoma clone stably expressing firefly luciferase, by measuring luciferase activity.

Analysis of in vivo nuclear factor-kappaB activation during liver inflammation in mice: prevention by catalase delivery.

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays crucial roles in inflammation, immunity, cell proliferation, and apoptosis. Until now, there have been few studies of NF-kappaB activation in whole animals because of experimental difficulties. Here, we show that mice receiving a simple injection of plasmid vectors can be used to examine NF-kappaB activation in the liver.

Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase.

Hydrogen peroxide may aggravate the peritoneal dissemination of tumor cells by activating the expression of a variety of genes. In this study, we used pegylated catalase (PEG-catalase) to examine whether prolonged retention of catalase activity within the peritoneal cavity is effective in inhibiting peritoneal dissemination in mouse models. Murine B16-BL6 cells or colon 26 cells labeled with firefly luciferase gene were inoculated intraperitoneally into syngeneic mice.

Inhibition of peritoneal dissemination of tumor cells by single dosing of phosphodiester CpG oligonucleotide/cationic liposome complex.

Although unmethylated CpG dinucleotide-containing oligodeoxynucleotides (CpG ODN) are able to inhibit tumor metastasis through the induction of antitumor immunity, their stability and delivery to antigen presenting cells needs to be improved. In this study, we formulated a CpG ODN complex with cationic liposomes (CpG ODN-lipoplex) and its antitumor activity was evaluated in peritoneal dissemination models of tumor cells stably labeled with firefly luciferase gene. A single intraperitoneal administration of CpG ODN-lipoplex greatly reduced the number of tumor cells to 0.