Folate-targeted supramolecular vesicular aggregates as a new frontier for effective anticancer treatment in in vivo model

Supramolecular vesicular aggregates (SVAs), made up by self-assembling liposomes and polyasparthydrazide co-polymers conjugated to folic acid molecules were extensively investigated in this manuscript as potential active targeting formulation for anticancer drug delivery. Folate-targeted systems (FT-SVAs) were used to treat breast cancer and to further proof the potential in vivo administration of these systems for the therapeutic treatment for several aggressive solid tumors. The physicochemical and technological parameters of FT-SVAs are suitable for their potential in vivo administration. The chemotherapeutic activity of GEM-loaded FT-SVAs was increased during in vivo experiments. NOD-SCID mice bearing MCF-7 human xenograft is used as breast cancer model. The measurement of the volume and weight of tumor masses decreased when animal models are treated by using GEM-loaded FT-SVAs, compared to data obtained by using GEM-loaded mPEG-SUVs and the free form of GEM. An almost complete regression of the tumor (∼0.2 cm3) was observed in NOD-SCID mice bearing MCF-7 human xenografts treated by GEM-loaded FT-SVAs due to the noticeable improvement of GEM pharmacokinetic parameters provided by FT-SVAs with respect to native anticancer drug. The obtained data showed that supramolecular systems could represent an innovative drug delivery system by self-assembling liposomes and biocompatible polymers to be potentially used for anticancer treatment.

Graphical abstractSchematic description of folate-targeted supramolecular vesicular aggregates (FT-SVAs) made up by self-assembling DPPC, cholesterol, and PAHy-C4-Folate in a supramolecular vesicular aggregates. FT-SVAs were carried out by combining thin layer evaporation method and extrusion procedure to finally obtain suitable colloidal systems for systemic injection. Gemcitabine hydrochloride (GEM) is loaded inside SVAs by using remote loading procedure. An acidic internal pH gradient was carried out inside SVAs to increase the loading efficiency of formulation. The intravenous injection of GEM-loaded FT-SVAs in NOD-SCID mice bearing MCF-7 human xenograft provides the decrease of both tumor volume and weight compared to saline solution, free GEM, PEGylated liposomes, and untargeted SVAs. In vivo anticancer activity of GEM-loaded FT-SVAs seems to encourage a potential therapeutic use of this formulation in anticancer therapy.Figure optionsDownload full-size imageDownload high-quality image (162 K)Download as PowerPoint slide