Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals.

Globally, breast cancer is the second leading cause of cancer-related mortality among women, with approximately 1.4 million new cases diagnosed annually. Associated genetic perturbations are emerging in the face of intense scientific enquiry, facilitating its classification, prognostication and treatment. RNAi, utilizing siRNA, is a powerful treatment strategy to silence disease-causing genes. However, therapeutic siRNA instability and poor cellular uptake have limited its clinical application, necessitating the use of nanocarriers. In this review, we highlight the RNAi mechanism, HER-2/neu and MYC as breast cancer gene targets, and nonviral nanocarriers as potentially safe and efficient delivery systems.

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The overexpression of the human epidermal growth factor 2 (HER2/neu) oncogene is predictive of adverse breast cancer prognosis. Silencing the HER2/neu overexpression using siRNA may be an effective treatment strategy. Major requirements for siRNA-based therapy are safe, stable, and efficient delivery systems to channel siRNA into target cells. This study assessed the efficacy of cationic lipid-based systems for the delivery of siRNA. Cationic liposomes were formulated with equimolar ratios of the respective cholesteryl cytofectins, 3β-N-(N′, N′-dimethylaminopropyl)-carbamoyl cholesterol (Chol-T) or N, N-dimethylaminopropylaminylsuccinylcholesterylformylhydrazide (MS09), with the neutral helper lipid, dioleoylphosphatidylethanolamine (DOPE), with and without a polyethylene glycol stabilizer. All cationic liposomes efficiently bound, compacted, and protected the therapeutic siRNA against nuclease degradation. Liposomes and siRNA lipoplexes were spherical, <200 nm in size, with moderate particle size distributions (PDI < 0.4). The siRNA lipoplexes exhibited minimal dose-dependent cytotoxicity and effective HER2/neu siRNA transfection in the HER2/neu overexpressing SKBR-3 cells. The non-PEGylated Chol-T-siRNA lipoplexes induced the highest HER2/neu silencing at the mRNA (10000-fold decrease) and protein levels (>111.6-fold decrease), surpassing that of commercially available Lipofectamine 3000 (4.1-fold reduction in mRNA expression). These cationic liposomes are suitable carriers of HER2/neu siRNA for gene silencing in breast cancer.