CARBON NANOMATERIALS DERIVED FROM ORGANIC SOURCES FOR DRUG DELIVERY AND THERAPY

Abstract

Remotely triggered drug delivery using nanoparticles is an area of great interest for targeted therapy to fight cancer. We developed photoresponsive nanoparticles to remotely initiate the release of doxorubicin (DOX) to 3D cultured human breast cancer cells (MCF-7) via NIR two-photon excitation (TPE) using carbon nanomaterials (CNMs). The drug loading capacity of CND-P was measured to be 0.98 w/w with the ability to release DOX via two-photon excitation (TPE). The biocompatible CNMs showed 88% cell viability at concentrations as high as 1100 μg/mL. The combined chemo and photothermal therapeutic effect of the DOX-loaded CNMs resulted in the death of 78% of the MCF-7 cells compared to 59% with DOX alone. Apart from extracellular pathogens, a common theme in the persistence of microbial infections involves intracellular survival of microbial pathogens within their host cells. To destroy such a recalcitrant pathogen, an intracellular infection of the cultured epithelial cell-line H413 with the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) was used. The conjugated CNMs were rapidly internalized into the cultured cells, reaching almost 90% uptake within 3 hours of the challenge, resulting in significantly increased inhibition of intracellular P. gingivalis compared to metronidazole alone. Conjugated CNMs and the drug doxorubicin (DOX) developed to release DOX from the surface of CNMs into cell nuclei with the use of ultrasound (ULS) as a trigger. The amino-acid derived green-emitting CNMs with high quantum yield (40%) showed excellent drug loading efficiency (97% w/w). The on-demand drug release was validated by taking advantage of the fluorescent properties of the CNMs using both confocal laser scanning microscopy and time-correlated single-photon counting techniques. Exposure of conjugated CNMs to 180 s of ULS enhanced its efficiency by 26.32 % compared to DOX alone.