Glioblastoma multiforme is the most lethal intrinsic brain tumor. Even with the existing treatment regimen of surgery, radiation, and chemotherapy, the median survival time is only 15–23 months. The invasive nature of this tumor makes its complete removal very difficult, leading to a high recurrence rate of over 90%. Drug delivery to glioblastoma is challenging because of the molecular and cellular heterogeneity of the tumor, its infiltrative nature, and the blood–brain barrier. Understanding the critical characteristics that restrict drug delivery to the tumor is necessary to develop platforms for the enhanced delivery of effective treatments. In this review, we address the impact of tumor invasion, the molecular and cellular heterogeneity of the tumor, and the blood–brain barrier on the delivery and distribution of drugs using potential therapeutic delivery options such as convection-enhanced delivery, controlled release systems, nanomaterial systems, peptide-based systems, and focused ultrasound.

Salmonellosis associated with consumption of mangoes have been traced back to the use of contaminated wash water. This highlights the critical role of wash water disinfection in mango processing, affecting its quality, and safety. Moreover, steps unique to the post-harvest handling of mangoes also create a conducive environment for internalization of pathogens into the fruit pulp. Currently, no effective treatment exists to eliminate internalized pathogens from mangoes. Therefore, it is critical to prevent contamination on the fruit to avert pathogen internalization. So the present study evaluated the efficacy of chlorine (200 ppm), peroxyacetic acid (80 ppm), and chlorine dioxide (5 ppm) for reducing Salmonella populations on mangoes and in wash water under simulated mango packing house conditions. Nalidixic-acid resistant isolates of Salmonella Montevideo, S. Newport, S. Baildon, S. Braenderup, and S. Poona were used in this study. Disinfectants were added to inoculated wash water (ca. 7 log CFU/ml) and mangoes (var. Atualfo and Tommy Atkins) were washed under simulated dump tank wash (24°C for 2 min), hot water treatment (46°C for 75 and 110 min), and hydrocooling conditions (21°C for 30 min). Wash water and mangoes were collected at different times for microbiological analysis. Additionally, residual disinfectant concentration was monitored throughout the study. All the three disinfectant tested were effective in significantly reducing Salmonella populations in wash water and on mangoes during dump tank wash, hot water treatment, and hydrocooling (p ≤ 0.05). Specifically, no Salmonella was detected from samples treated with 200 ppm chlorine and 80 ppm PAA. On the other hand, Salmonella was consistently recovered from mango and water samples treated with chlorine dioxide (5 ppm). This reduced antimicrobial efficacy can be attributed to the sharp decline in residual chlorine dioxide concentrations in wash water. Further, reductions in residual chlorine and PAA concentrations were also observed over time. Therefore, to ensure the sustained antimicrobial activity of chlorine and PAA, it is critical to regularly monitor and replenish the disinfectant in wash water. However, given the laboratory scale of these experiments, further validation of these results on a commercial scale are warranted.

Consumption of raw mangoes has led to multiple Salmonella-associated foodborne outbreaks in the United States. Although several studies have investigated the epiphytic fitness of Salmonella on fresh produce, there is sparse information available on the survival of Salmonella on mangoes under commercial handling and storage conditions. Hence, the objective of the study was to evaluate the survival of Salmonella on mangoes under ambient conditions simulating the mango packing house and importer facility. Further, the ability of the pathogen to adhere and attach on to the mango fructoplane was also investigated. For the attachment assays, mango skin sections were inoculated with fifty microliters of S. Newport suspension (6.5 log CFU/skin section) and minimum time required for adhesion and attachment were recorded. With the survival assays, unwaxed mangoes were spot inoculated with the Salmonella cocktail to establish approximately 4 and 6.5 log CFU/mango. The fruits were then subjected to different storage regimens simulating fruit unloading, waxing, and storage at the packing house and ripening and storage at the importer facility. Results of our study reveal that Salmonella was able to adhere on to the fructoplane immediately after contact. Further, formation of attachment structures was seen as early as 2 min following inoculation. With the survival assays, irrespective of the inoculum levels, no significant increase or decrease in pathogen population was observed when fruit were stored either at ambient (29–32^∘C and RH 85–95%, for 48 h), ripening (20–22^∘C and RH 90–95% for 9 days) or refrigerated storage (10–15^∘C and 85–95% for 24–48 h) conditions. Therefore, once contaminated, mangoes could serve as potential vehicles in the transmission of Salmonella along the post-harvest environment. Hence development and adoption of effective food safety measures are warranted to promote the microbiological safety of mangoes.

Currently, there is a great interest in nanoparticle-based vaccine delivery. Recent studies suggest that nanoparticles when introduced into the biological milieu are not simply passive carriers but may also contribute immunological activity themselves or of their own accord. For example there is considerable interest in the biomedical applications of one of the physiologically-based inorganic metal oxide nanoparticle, zinc oxide (ZnO). Indeed zinc oxide (ZnO) NP are now recognized as a nanoscale chemotherapeutic or anticancer nanoparticle (ANP) and several recent reports suggest ZnO NP and/or its complexes with drug and RNA induce a potent antitumor response in immuno-competent mouse models. A variety of cell culture studies have shown that ZnO NP can induce cytokines such as IFN-γ, TNF-α, IL-2, and IL-12 which are known to regulate the tumor microenvironment. Much less work has been done on magnesium oxide (MgO), cobalt oxide (Co₃O₄), or nickel oxide (NiO); however, despite the fact that these physiologically-based metal oxide NP are reported to functionally load and assemble RNA and protein onto their surface and may thus also be of potential interest as nanovaccine platform. Here we initially compared in vitro immunogenicity of ZnO and Co₃O₄ NP and their effects on cancer-associated or tolerogenic cytokines. Based on these data we moved ZnO NP forward to testing in the ex vivo splenocyte assay relative to MgO and NiO NP and these data showed significant difference for flow cytometry sorted population for ZnO-NP, relative to NiO and MgO. These data suggesting both molecular and cellular immunogenic activity, a double-stranded anticancer RNA (ACR), polyinosinic:poly cytidylic acid (poly I:C) known to bind ZnO NP; when ZnO-poly I:C was injected into B16F10-BALB/C tumor significantly induced, IL-2 and IL-12 as shown by Cohen’s d test. LL37 is an anticancer peptide (ACP) currently in clinical trials as an intratumoral immuno-therapeutic agent against metastatic melanoma. LL37 is known to bind poly I:C where it is thought to compete for receptor binding on the surface of some immune cells, metastatic melanoma and lung cells. Molecular dynamic simulations revealed association of LL37 onto ZnO NP confirmed by gel shift assay. Thus using the well-characterized model human lung cancer model cell line (BEAS-2B), poly I:C RNA, LL37 peptide, or LL37-poly I:C complexes were loaded onto ZnO NP and delivered to BEAS-2B lung cells, and the effect on the main cancer regulating cytokine, IL-6 determined by ELISA. Surprisingly ZnO-LL37, but not ZnO-poly I:C or the more novel tricomplex (ZnO-LL37-poly I:C) significantly suppressed IL-6 by >98–99%. These data support the further evaluation of physiological metal oxide compositions, so-called physiometacomposite (PMC) materials and their formulation with anticancer peptide (ACP) and/or anticancer RNA (ACR) as a potential new class of immuno-therapeutic against melanoma and potentially lung carcinoma or other cancers.

The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal–regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.

The aim of this study was to investigate the distribution, tolerance, and anticancer and antiviral activity of Zn-based physiometacomposites (PMCs). Manganese, iron, nickel and cobalt-doped ZnO, Zn...