Controlled release of targeted chemotherapeutic drug dabrafenib for melanoma cancers monitored using surface-enhanced Raman scattering (SERS) spectroscopy

Abstract

The advanced skin cancer melanoma, which is primarily caused by the mutation of BRAF gene, has a high mortality rate and requires high doses of chemotherapeutic drugs. To mitigate the drug toxicity to healthy cells and other side effects, the development of alternative modes of treatment has been extensively sought after. Herein, we describe a new targeted drug delivery system with controlled release, based on nanoparticle nanocarriers functionalized with folate and transferrin ligands for recognition of the respective receptors overexpressed in cancer cell membrane. We have investigated the immobilization of a new drug dabrafenib onto the nanocarriers and its controlled release, aided with surface-enhanced Raman scattering (SERS) spectroscopy which affords ultra-sensitive in situ measurement ability owing to the high signal amplification, associated with strong plasmonic fields of the nanocarrier gold nanoparticle (AuNP) cores. The nanocarriers were equipped with Raman reporters: mercaptobenzoic acid (MBA) and para-aminothiophenol (PATP) forming a mixed thiolate monolayer shell on AuNPs. The dabrafenib was covalently attached to MBA via an amide bond which is pH sensitive and enables the drug release at lower pH encountered in cancer cells. This arrangement in the drug binding to the nanocarrier protects the dabrafenib amine group against deactivation until the drug release in the target tumor cells.