Enhancement of the Cytotoxic Effect of Anticancer Agent by Cytochrome c Functionalised Hybrid Nanoparticles in Hepatocellular Cancer Cells

Treatment of hepatocellular cancer with chemotherapeutic agents has limited successin clinical practice and their efficient IC50 concentration would require extremely highdoses of drug administration which could not be tolerated due to systemic side effects.In order to potentiate the efficacy of anticancer agents we explored the potentialof co-treatment with pro-apoptotic Cytochrome c which activates the apoptoticpathway downstream of p53 that is frequently mutated in cancer. To this end weused hybrid iron oxide-gold nanoparticles as a drug delivery system to facilitate theinternalisation of Cytochrome c into cultured HepG2 hepatocellular carcinoma cells.Our results showed that Cytochrome c can be easily conjugated to the gold shell ofthe nanoparticles which are readily taken up by the cells. We used Cytochrome cin concentration (0.2μgmL-1) below the threshold required to induce apoptosis onits own. When the conjugate was administered to cells treated by doxorubicin, itsignificantly reduced its IC50 concentration from 9μgmL-1 to 3.5μgmL-1 as detectedby cell viability assay, and the efficiency of doxorubicin on decreasing viability ofHepG2 cells was significantly enhanced in the lower concentration range between0.01μgmL-1 to 5μgmL-1. The results demonstrate the potential of the application oftherapeutic proteins in activating the apoptotic pathway to complement conventionalchemotherapy to increase its efficacy. The application of hybrid iron oxide-goldnanoparticles can also augment the specificity of drug targeting and could serve as amodel drug delivery system for pro-apoptotic protein targeting and delivery.

Effective network security monitoring: from attribution to target-centric monitoring

Network security monitoring remains a challenge. As global networks scale up, in terms of traffic, volume and speed, effective attribution of cyber attacks is increasingly difficult. The problem is compounded by a combination of other factors, including the architecture of the Internet, multi-stage attacks and increasing volumes of nonproductive traffic. This paper proposes to shift the focus of security monitoring from the source to the target. Simply put, resources devoted to detection and attribution should be redeployed to efficiently monitor for targeting and prevention of attacks. The effort of detection should aim to determine whether a node is under attack, and if so, effectively prevent the attack. This paper contributes by systematically reviewing the structural, operational and legal reasons underlying this argument, and presents empirical evidence to support a shift away from attribution to favour of a target-centric monitoring approach. A carefully deployed set of experiments are presented and a detailed analysis of the results is achieved.