V.A. Petrenko, V.P. Torchilin
Keywords: metastatic breast cancer, precise nanomedicines, phage display, landscape phage, targeted drug delivery, Paclitaxel
Summary:Breast cancer is one of the most common cancers in the USA. Despite the increase of relative survival rate of women with breast cancer for the last decades, it is still low (~26%, 5 years) in patients diagnosed at late stages of disease. A common cause of breast cancer mortality is metastasis to lymph nodes, lung, liver, bone and brain. One of the most widely used drug for the treatment of metastatic breast cancer (MBC) is paclitaxel (PTX). Beside its high anticancer efficacy, clinical applications of PTX are limited due to its insolubility in water, appeared hemolysis, and other serious complications, such as resistance to chemotherapy and subsequent progression of disease, which are observed in metastatic patients. The problem of poor solubility and bioavailability of PTX was solved in part by co-condensation of albumin and paclitaxel in Abraxane (Abraxis Oncology), which received FDA approval for clinical use in 2005. However, the problem of nonspecific toxicity of PTX still exist. To enhance therapeutic efficacy and decrease side effects of PTX, encapsulation of the drug in micelles and targeting of the nanomedicines towards the vasculature and tumor cells was proposed. Using our proprietary "Landscape Phage Technology", our team developed a new class of Phage-Programmed Anticancer Nanomedicines: "Paclitaxel-Loaded PEG-PE–Based Micells, Targeted to Metastatic Breast Cancer cells by Tumor-Specific Landscape Phage Fusion Proteins" shortly—“P-micelles". We developed potential breast cancer nanomedicines, which showed selective toxicity to target cancer cells rather than nontarget, non cancer cells in vitro. In vivo, they triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathologic changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment.