Graphene and single-walled carbon nanotubes were used to deliver the natural low-toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems.
Carbon-shelled, iron-based magnetic nanoparticles (C/Fe MNPs) were found to act as strong heat generating agents when exposed to radio-frequency (RF) energy with the ability to thermally destroy cancer cells. In order to efficiently deliver MNPs to cancer cells and to enhance the effectiveness of the RF treatment, human epidermal growth factor (EGF) was bioconjugated with the C/Fe MNPs for their specific delivery to two cancer cell lines, MCF-7 breast cancer cells and Panc-1 pancreatic cancer cells, respectively. These cell lines overexpress the epidermal growth factor receptors (EGFRs) and were used in this study as models. EGF-MNPs have shown higher surface binding efficiency towards the MCF-7 cells based on the comparative z-potential measurements. Confocal optical microscopy further confirmed that EGF-bioconjugated MNPs highly accumulated around and inside of these cancer cells. RF treatment was found to destroy 92.8% of MCF-7 breast cancer cells during 10 minutes of treatment when EGF was bound to the nanoparticles, while 37.3% of cells died when MNPs alone were used in identical conditions. Panc-1 cancer cells exhibit a higher resistance than MCF-7 cells when they were exposed to MNPs or RF treatment. Cytotoxicity studies demonstrated that the EGF-C/Fe MNP bioconjugates present lower toxicity compared to the C/Fe MNP. Caspase assay studies demonstrated that the MCF-7 cancer cells underwent an apoptotic process by the caspase 3 deficiency pathway showing no evidence of morphological changes such as membrane blebbing.
Functionalized graphene (fGn) has been used to deliver the low toxicity plant product, gambogic acid (GA), to cervical, ovarian, and prostate cancer cells, and the relative cytotoxicity of this complex when compared to delivery of drug alone has been evaluated. In this study, we analyzed the characteristics of the GA + fGn complex, including pH-sensitive release of the drug from the nanomaterial. We then compared the in vitro effects of GA and GA + fGn on the growth inhibition and apoptosis in the above three cancer cell types. We found that GA, when delivered as a GA/fGn complex was more effective at inhibiting cell proliferation, initiating cell cycle arrest and inducing apoptosis in HeLa, NCI/ADR-RES, and PC-3 cancer cell lines compared to delivery of drug alone. Overall, our results indicate that this novel GA/fGn nanocomplex has the ability to inhibit proliferation and induce apoptosis in several different organ-derived cancer cells, and could have potential as a new drug delivery strategy in cancer chemotherapy.
A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 μg mL
−1
and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40%) were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.