A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe 2

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Silver is an effective antimicrobial agent with low toxicity, which is important especially in the treatment of burn wounds where transient bacteremia is prevalent and its fast control is essential. Drugs releasing silver in ionic forms are known to get neutralized in biological fluids and upon long-term use may cause cosmetic abnormality, e.g., argyria and delayed wound healing. Given its broad spectrum activity, efficacy and lower costs, the search for newer and superior silver based antimicrobial agents is necessary. Among the various options available, silver nanoparticles have been the focus of increasing interest and are being heralded as an excellent candidate for therapeutic purposes. This report gives an account of our work on development of an antimicrobial gel formulation containing silver nanoparticles (SNP) in the size range of 7-20 nm synthesized by a proprietary biostabilization process. The typical minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against standard reference cultures as well as multidrug-resistant organisms were 0.78-6.25 microg/mL and 12.5 microg/mL, respectively. Gram-negative bacteria were killed more effectively (3 log(10) decrease in 5-9 h) than Gram-positive bacteria (3 log(10) decrease in 12 h). SNP also exhibited good antifungal activity (50% inhibition at 75 microg/mL with antifungal index 55.5% against Aspergillus niger and MIC of 25 microg/mL against Candida albicans). When the interaction of SNP with commonly used antibiotics was investigated, the observed effects were synergistic (ceftazidime), additive (streptomycin, kanamycin, ampiclox, polymyxin B) and antagonistic (chloramphenicol). Interestingly, SNP exhibited good anti-inflammatory properties as indicated by concentration-dependent inhibition of marker enzymes (matrix metalloproteinase 2 and 9). The post agent effect (a parameter measuring the length of time for which bacterial growth remains suppressed following brief exposure to the antimicrobial agent) varied with the type of organism (e.g., 10.5 h for P. aeruginosa, 1.3 h for Staphylococcus sp. and 1.6 h for Candida albicans) indicating that dose regimen of the SNP formulation should ensure sustained release of the drug. To meet this requirement, a gel formulation containing SNP (S-gel) was prepared. The antibacterial spectrum of S-gel was found to be comparable to that of a commercial formulation of silver sulfadiazine, albeit at a 30-fold less silver concentration. As part of toxicity studies, localization of SNP in Hep G2 cell line, cell viability, biochemical effects and apoptotic/necrotic potential were assessed. It was found that SNP get localized in the mitochondria and have an IC(50) value of 251 microg/mL. Even though they elicit an oxidative stress, cellular antioxidant systems (reduced glutathione content, superoxide dismutase, catalase) get triggered and prevent oxidative damage. Further, SNP induce apoptosis at concentrations up to 250 microg/mL, which could favor scarless wound healing. Acute dermal toxicity stu...

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Honokiol ((3’,5-di-(2-propenyl)-1,1’-biphenyl-2,2’-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anti-cancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications.

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Bladder cancer is often associated with recurrence and progression to invasive metastatic disease that have palliative therapeutic options. The use of traditional chemotherapeutic agents for bladder cancer management often suffer from toxicity and resistance concerns. This emphasizes the need for development of safer, natural, non-toxic compounds as chemotherapeutic/chemopreventive agents. Curcumin (diferuloylmethane) is a natural compound that has been known to possess anti-cancer properties in various cancers, including bladder cancer. However, the biological targets of curcumin are not well defined. Recently, it has been proposed that curcumin may mediate epigenetic modulation of expression of microRNAs (miRNAs). In this report, we define for the first time, that curcumin directly induces a tumor-suppressive miRNA, miR-203, in bladder cancer. miR-203 is frequently downregulated in bladder cancer due to DNA of its promoter. We studied the functional significance of miR-203 in bladder cancer cell lines and found that miR-203 has tumor suppressive properties. Also, we define Akt2 and Src as novel miR-203 targets in bladder cancer. Curcumin induces hypomethylation of the miR-203 promoter and subsequent upregulation of miR-203 expression. This leads to downregulation of miR-203 target genes Akt2 and Src that culminates in decreased proliferation and increased apoptosis of bladder cancer cells. This is the first report that shows a direct effect of curcumin on inducing epigenetic changes at a miRNA promoter with direct biological consequences. Our study suggests that curcumin may offer a therapeutic advantage in the clinical management of refractory bladder cancer over other standard treatment modalities.

Pancreatic cancer (PC) has the worst prognosis among all cancers due to its late diagnosis and lack of effective therapies. Therefore, identification of novel gene targets, which are differentially expressed in PC and functionally involved in malignant phenotypes, is critical to achieve early diagnosis and development of effective therapeutic strategies. We have shown previously that MUC4, an aberrantly overexpressed transmembrane mucin, promotes growth, invasion and metastasis of PC cells, thus underscoring its potential as a clinical target. Here, we report a novel microRNA (miRNA)-mediated mechanism underlying aberrant expression of MUC4 in PC. We demonstrate that the 3' untranslated region of MUC4 contains a highly conserved miRNA-150 (miR-150) binding motif and its direct interaction with miR-150 downregulates endogenous MUC4 protein levels. We also show that miR-150-mediated MUC4 downregulation is associated with a concomitant decrease in human epidermal growth factor receptor 2 and its phosphorylated form, leading to reduced activation of downstream signaling. Furthermore, our findings demonstrate that miR-150 overexpression inhibits growth, clonogenicity, migration and invasion and enhances intercellular adhesion in PC cells. Finally, our data reveal a downregulated expression of miR-150 in malignant pancreatic tissues, which is inversely associated with MUC4 protein levels. Altogether, these findings establish miR-150 as a novel regulator of MUC4 and a tumor suppressor miRNA in PC.