Targeting breast cancer using pirarubicin loaded vasoactive intestinal peptide grafted sterically stabilized micelles

Cancer is considered as one of the most fatal illnesses in the modern world and millions of people every year suffer from it. Breast cancer alone is responsible for thirty percent of all new cancer cases among women. Several treatment options are available for breast cancer, including: surgery, radiation therapy, hormone therapy, immunotherapy and chemotherapy. Chemotherapy is a common treatment which systemically delivers anticancer agents to suppress cancer cells. Conventional chemotherapy does not allow selective targeting and causes adverse side effects. Thus they cause serious side effects. Pirarubicin is a new generation of doxorubicin. Like other anthracyclines, its clinical use has been hampered because of cardiotoxicity and the formation of multiple drug resistance (even though it is less toxic and more potent than other family members). Nanoparticle-based drug delivery systems are of great potential in treating cancer. Targeted drug delivery systems are known to be efficient ways to minimize the side effects of anticancer drugs. If a biomarker is known to be available in the targeted cancer area, active targeted drug delivery can be performed. Considering the fact that receptors for vasoactive intestinal peptide (VIP-R) are overexpressed in breast cancer, we attached VIP to the surface of biodegradable nanoparticles containing pirarubicin for active targeting of a phospholipid made drug delivery to breast cancer. It was found to be more effective than passively targeted and free pirarubicin in MCF-7 human breast cancer cell lines and in vivo mice models. Different factors have been reported to contribute to MDR in clinical usage of anthracyclines. Among them are Nuclear factor-kappa B (NF-κB) transcription factors. Several research studies have unveiled that curcumin can down-regulate MDR proteins and suppress the activity of NF-κB. Curcumin is known to be able to reduce NF-κB, however, despite the effectiveness of curcumin against numerous human disorders, its poor water solubility is one of the key issues that limit its therapeutic efficacy in the clinic. Nano-sized drug delivery systems can help to overcome these limitations as well. Considering these facts, this study explored the effects of co-administration of nano-curcumin on anticancer effect of nano-pirarubicin. The cytotoxicity was researched in co-treatment, prior and posterior administration of C-SSM and P-SSM. NF-κB level was found to be reduced in co-adminestration of formulations on MCF-7.