Development of a novel nanoformulation against the colorectal cancer.

Colorectal cancer (CRC) with high metastasis rates has been known as a major cause of death worldwide. Lack of the specificity and insufficient concentrations of traditional chemotherapeutics at tumor site and their severe adverse effects necessitate development of new treatment strategies such as designing suitable nanocarriers for delivery of drugs, improving their pharmacological profiles and reducing adverse effects. We have developed a platform based on the poly-ursolic acid (poly-UA), a polymeric system with potential anticancer effect. Following the self-assembly of poly-UA into the nanoparticles (NPs), they were applied for delivery of mithramycin A (Mith-A), a promising candidate for CRC therapy, however, with some limitations such as rapid clearance and serious side effects. Mith-A-loaded poly-UA NPs with suitable physicochemical properties and efficient drug entrapment, released Mith-A in a controlled manner and provided suitable toxicity against the CT-26 colorectal cancer cells, increased accumulation in tumor, and protection against the detrimental features of the disease. Poly-UA NPs demonstrated therapeutic efficiency (in vivo and in vitro) by themselves. The prepared NPs induced no remarkable alteration of body weights or damages to the major organs in animals bearing tumor indicating the safety of NPs. The bioactive nanoformulation along with improving the pharmacological profile of Mith-A could provide a synergistic toxicity against the CRC.