Amro El Badawy
Silver and silver-based products are known to cause cytotoxic effects to both microbes and eukaryotic cells. Because of this property, silver nanoparticles (AgNPs) are being studied for their potential in targeted tumor treatments. Previous studies with microbes suggest that AgNPs with cationic capping agents possess enhanced cytotoxicity by virtue of Coulombic attraction between the nanoparticle and the negatively-charged cell wall. Since animal cells possess similar negatively-charged plasma membranes, this research hypothesized that human cells would be more susceptible to positively-charged AgNPs than to negatively-charged AgNPs. To investigate this hypothesis, cancerous cervical cells (HeLa) and healthy fibroblast cells (3T3) were subjected to treatments of 40 nm diameter AgNP with branched polyethylenimine (AgBPEI, ζ = + 69 mV) and citrate (AgCit, ζ = -49 mV) capping agents. AgNO3 was also tested to compare AgNP toxicity to that of ionic silver (Ag+). An alamarBlue® viability assay was used to quantify the cytotoxicity of the treatments relative to an untreated control group. AgBPEI displayed a lower LD50 (median lethal dose) than both Ag+ and AgCit to both cell lines. This suggests AgNP toxicity is not solely from Ag+ dissolution, and also ostensibly supports the initial hypothesis (compared to AgCit, AgBPEI was approximately 84% more cytotoxic to HeLa cells and about 65% more cytotoxic to fibroblast cells). However, significant AgCit aggregation was observed in culture media, which obfuscates surface charge-based toxicity effects because larger diameter AgNPs are less cytotoxic. In this way, size-dependent toxicity must also be considered. While this does not allow for conclusions regarding the sole influence of surface charge, and therefore the hypothesis cannot be directly supported, results do not negate its validity. Ultimately, since AgBPEI is more stable than AgCit under in vitro conditions and is more prone to Coulombically interact with cancer cells, researchers investigating AgNPs for targeted tumor treatments should utilize AgBPEI over AgCit on the premise of enhanced bioavailability. This research will continue over the summer of 2017 to retest AgBPEI against a negatively-charged AgNP that is stable in test media. To this end, a silver nanoparticle coated with carboxyl (lipoic acid, ζ < 0 mV) has been ordered. This would isolate surface charge as the only independent variable and eliminate aggregation effects as a source of error, thus allowing for verification of the existing hypothesis.
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