Mutations of the BRAF gene are associated with many human cancers including melanoma, breast cancer, gliomas, and others. The BRAF gene encodes the protein B-Raf, or serine/threonine-protein kinase B-Raf, an important signaling protein in cellular growth. The current treatment options for these cancers include surgery, chemotherapy, and radiation. Dabrafenib is a drug used to inhibit B-Raf proteins and has shown promising inhibition of cancer cell growth with a specific BRAF V600E mutation. The goal of our study is to develop a controlled release delivery system for dabrafenib avoiding its devastating side effects and damage to healthy tissues. In this work, we have utilized gold nanoparticles as the carriers for dabrafenib delivery. The gold nanoparticles were functionalized with a self-assembled monolayer (SAM) of mercaptobenzoic acid (MBA) and dabrafenib covalently bound via an amide bond to the MBA-SAM. This bond is stable at physiological pH but it is cleaved at a low pH. The surface-enhanced Raman spectroscopy (SERS) indicates that at a pH of 5.5, the MBA signals increase in intensity over time while no change in MBA signal was observed at physiological pH of 7.4. This increase of MBA signal is due to the amide bond breaking and drug release, resulting in the MBA exposure. The <i>in vitro</i> studies involved the breast cancer cell line MDA-MB-231. The cells were transfected with drug-loaded functionalized AuNPs. The Muse Cell Analyzer was used for assessment of phosphorylated histone H2AX via capillary-based flow cytometry. The results were analyzed using multi-color DNA damage module of the Muse software analysis package. The proposed new controlled drug release system based on gold nanoparticle carriers can be utilized for targeted delivery of dabrafenib in treatment of melanoma, breast cancer, and other high-grade or metastasized BRAF cancers.

Chemotherapeutic drug delivery system based on gold nanoparticle carriers for cancer treatment

254th National Meeting (2017)

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