Nanoliposomes as the adjuvant delivery systems in cancer immunotherapy.

Cancer immunotherapy is one of the commonly used methods in the treatment of cancer. The aim of this approach is to strengthen or restore immune function for effective diagnosis of aberrant cells antigens. For this reason, cancer specific peptides or proteins are used as antigens to induce an immune response capable of removing cancer cells. Liposomal formulations are an important carrier system frequently used for delivery of antigen because the specific properties of this component such as lipid composition, charge, size, encapsulation of antigens, or adjuvants can be changed. Among different types of liposomal formulations, the use of cationic and pH-sensitive nanoliposomes has been markedly increased for liposome-based vaccines. In this review, we describe the properties of nanoliposomes as delivery systems for cancer immunotherapy.

The effect of RGD-targeted and non-targeted liposomal Galbanic acid on the therapeutic efficacy of pegylated liposomal doxorubicin: From liposomal preparation to in-vivo studies.

The anti-cancer therapeutic application of Galbanic acid (Gba) as a strong antiangiogenic sesquiterpene coumarin has been limited due to its low water solubility. This issue necessitates developing new liposomal formulations for the efficient delivery of Gba in vivo. In this study, various liposomal formulations were prepared by a thin-film hydration method, and Gba was incorporated into the liposomal bilayers, which consequently increased its release profile compared to formulations in our previous study prepared by remote loading methods. The most stable formulation with desired properties was selected and decorated with RGD peptide (cyclo [Arg-Gly-Asp-D-Tyr-Cys]) to target tumor vasculature actively. The fluorescently-labeled model liposomes showed that the targeting could improve the receptor-mediated endocytosis of the liposomes higher than those prepared in our previous study in vitro in human umbilical vein endothelial cells (HUVECs), which was confirmed by chicken chorioallantoic membrane angiogenesis (CAM) model in vivo. Although not significant, it also could increase the accumulation of liposomes in colon tumors. In BALB/c mice bearing colon cancer, not only non-targeted Gba liposomes but also even RGD-targeted ones combinatorial therapy with pegylated liposomal doxorubicin could improve the anti-tumor efficacy as compared to their monotherapy. These outcomes have strong consequences for cancer therapy.

Liposomal formulation of Galbanic acid improved therapeutic efficacy of pegylated liposomal Doxorubicin in mouse colon carcinoma.

Galbanic acid (Gba), a sesquiterpene coumarin, with strong antiangiogenic activity could serve as an excellent anti-cancer agent. However, Gba is a poor water-solube which hampered its clinical application. In this study, a pegylated liposomal Gba (PLGba) with HSPC/Cholesterol/mPEG2000-DSPE (56.2, 38.3, 5.3% molar ratio) was developed by the thin film hydration plus extrusion and calcium acetate gradient remote loading method, to address the issue of poor Gba solubility. Moreover, an integrin-targeting ligand (RGD peptide, cyclo[Arg-Gly-Asp-D-Tyr-Cys]) was post-inserted into liposomes in order to increase Gba cell delivery. Using fluorescently-labeled model liposomes, it was found that the targeting could improve the integrin-mediated cellular uptake of the liposomes in vitro in human umbilical vein endothelial cells (HUVECs), and in vivo as evidenced by chicken chorioallantoic membrane angiogenesis (CAM) model. It also could enrich the liposome accumulation in C26 tumor. Interestingly, co-treatment with PLGba and pegylated liposomal doxorubicin (PLD, also known as Doxil®) had a synergistic and antagonistic antiproliferative effect on the C26 tumor cell line and the normal HUVEC, respectively. In C26 tumor bearing BALB/c mice, the PLGba and PLD combinatorial therapy improved the antitumor efficacy of the treatment as compared to those of single agents. This results have clear implications for cancer therapy.