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

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.

Download Full-text

Controlled release of targeted anti-leukemia drugs azacitidine and decitabine monitored using surface-enhanced Raman scattering (SERS) spectroscopy

Mediterranean Journal of Chemistry ◽

10.13171/mjc64/01706081223-hepel ◽

2017 ◽

Vol 6 (4) ◽

pp. 125-132 ◽

Cited By ~ 3

Author(s):

Madison Smith ◽

Maria Hepel

Keyword(s):

Drug Delivery ◽

Folic Acid ◽

Controlled Release ◽

Drug Release ◽

Raman Scattering ◽

Cancer Cells ◽

Surface Enhanced Raman Scattering ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

Enhanced Raman Scattering

A new targeted drug delivery system with controlled release of anti-cancer drugs, azacitidine and decitabine, was investigated to enhance the efficacy of cancer treatment and reduce the effects of high drug toxicity to healthy tissues. The proposed drug nanocarriers are based on gold nanoparticles (AuNPs) modified with mercaptobenzoic acid (MBA) linker to enable the immobilization of azacitidine (AZA) and decitabine (DAC) on AuNPs in the form of AuNP@MBA/AZA,DAC entities. The cancer cell recognition was accomplished by covalently binding folic acid (FA) ligands to para-aminothiophenol (PATP) in the mixed SAM shell on gold nanoparticle nanocarriers, AuNP@MBA,PATP. The FA ligand was used due to the strong expression of folic acid receptors (FR) in the membrane of cancer cells. This enables the functionalized carriers to target only cancer cells owing to the efficient FA-FR binding property. The amide bonds between the linkers and azacitidine/decitabine are pH sensitive and undergo acid hydrolysis in a low pH environment of the cytosol in cancer cells. Using the solutions of different pH, the release of azacitidine/decitabine was monitored by surface-enhanced Raman scattering spectroscopy (SERS) measurements of the MBA Raman modes at 1586 cm-1 and 1074 cm-1 . At pH 7.4, the release of the drug was found to be negligible, while at pH 4.0 and 5.5 a continuous drug release was observed over 3 hours. The utilization of SERS monitoring for the drug release was based on the strong Raman signals which are generated by the MBA linker when it is bound to a plasmonic AuNP. During the immobilization of azacitidine/decitabine on AuNP carriers, the SERS signals are strongly reduced due to the shielding by drug molecules but they increase sharply upon the drug release confirming the amide bond breakage and successful drug delivery.

Download Full-text