The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel

Mesothelin, protein is frequently expressed in ovarian cancers. However, a full understanding of the biological functions of mesothelin is lacking. Here, we investigate the drug targeting potential of antibody conjugated modified half-generation poly (propylene imine) dendrimers i.e. immunodendrimers toward ovarian cancer with a model anti-cancer agent, paclitaxel (PTX). The synthesized plain 4.5G dendrimers as well as immunodendrimers were characterized by FT-IR, 1H-NMR, TEM, and flow cytometry. Immunodendrimers exhibited considerably reduced hemolytic-, hepato- and nephrotoxicity. MTT cytotoxicity, flow cytometry and cell morphology studies were conducted in OVACAR-3 and A-431 cell. We demonstrate that PTX loaded immunodendrimers reduced the tumor volume significantly. The biodistribution studies further confirmed the targeting efficiency and higher biodistribution of immunodendrimers into the mesothelin protein expressing ovarian cancer cells. The results concluded that the developed immunodendrimers have potential to deliver significantly higher amount of the bioactive and have improved therapeutic outcome.From the Clinical EditorThe authors investigated the drug targeting potential of antibody conjugated modified half-generation poly(propyleneimine) dendrimers toward ovarian cancer with a model anti-cancer agent, demonstrating delivery of significantly higher amount of paclitaxel (PTX) and improved therapeutic outcome.

The present investigation was aimed to develop and evaluate the anti-cancer potential of paclitaxel loaded poly(propylene imine) immunodendrimer. BALB/c mice were used as in vivo model for qualitative and quantitative assessment of toxicity, anti-cancer activity, and cancer targeting potential of immunodendrimer.Figure optionsDownload high-quality image (260 K)Download as PowerPoint slide