作者: Rad-Malekshahi, Mazda ; Movahed, Ali ; Rahimikian, Raha ; Mohammadi, Mohsen ; Bargahi, Afshar ; Mohseninia, Atefeh ; Reza Farzaneh, Mohammad ; Dehghani, Parva

Induction of tumor-specific CD8 + T cell responses is known as a major challenge for cancer vaccine development; here we presented a strategy to improve peptide nanofibers-mounted antitumor immune responses. To this end, peptide nanofibers bearing class I (Kb)-restricted epitope (Epi-Nano) were formulated with polyethylene imine backbone (Epi-Nano-PEI), and characterized using morphological and physicochemicalcharacterizationtechniques. Nanofibers were studied in terms of their uptake by antigen-presenting cells (APCs), antigen cross-presentation capacity, and cytotoxic activity. Furthermore, nanofibers were assessed by their potency to induce NLRP3 inflammasome-related cytokines and factors. Finally, the ability of nanofibers to induce tumor-specific CD8 T cells and tumor protection were investigated in tumor-bearing mice. The formulation of Epi-Nano with PEI led to the formation of short strand nanofibers with a positive surface charge, a low critical aggregation concentration (CAC), and an increased resistancetoproteolytic degradation. Epi-Nano-PEI was significantly taken up more efficiently by antigen-presenting cells (APCs), and was more potent in cross-presentation when compared to Epi-Nano. Moreover, Epi-Nano-PEI, in comparison to Epi-Nano, efficiently up-regulated the expression of NLRP3, caspase-1, IL-1b, IL18 and IL-6. Cell viability analysis showed that formulation of PEI with Epi-Nano not only abolished its cytotoxic activity, but surprisingly induced macrophage proliferation. Furthermore, it demonstrated that Epi-Nano-PEI triggered robust antigen-specific CD8⁺ T cell responses, and induced maximum antitumor response (tumor growth inhibition and prolonged survival) in tumor-bearing mice that were significantly higher compared to Epi-Nano. Taken together, the formulation of Epi-Nano with PEI is suggested as a promising strategy to improve nanofibers-mounted antitumor immune response.

2022-01-01·Bioorganic Chemistry2区 · 化学

Ofloxacin@Doxorubicin-Epirubicin functionalized MCM-41 mesoporous silica–based nanocarriers as synergistic drug delivery tools for cancer related bacterial infections

2区 · 化学

Article

作者: Oliveira, Elisabete ; Marcelo, Gonçalo A ; Duarte, Maria Paula ; Galhano, Joana

Mesoporous silica nanoparticles (MNs) emerged as new promising drug-delivery platforms capable to overcome resistance in bacteria. Dual loading of drugs on these nanocarriers, exploiting synergistic interactions between the nanoparticles and the drugs, could be considered as a way to increase the efficacy against resistant bacteria with a positive effect even at very low concentrations. Considering that patients with cancer are highly susceptible to almost any type of bacterial infections, in this work, nanocarriers mesoporous silica-based, MNs and MNs@EPI were synthetized and submitted to single and/or dual loading of antibiotics (ofloxacin - OFLO) and anticancer drugs (Doxorubicin - DOX; Epirubicin - EPI), and investigated regarding their antibacterial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis and Pseudomonas aeruginosa. Formulations containing ofloxacin such as MNs-OFLO, MNs-EPI + OFLO, MNs-DOX + OFLO and MNs@EPI + OFLO, present antibacterial activity in all bacterial strains tested. All these are more effective in E.coli with MIC and MBC values for MNs-OFLO, MNs-EPI + OFLO and MNs-DOX + OFLO of around 1 and 2 µg_nanomaterial/mL, corresponding to ofloxacin concentrations of 0.03, 0.02 and 0.04 µg/mL, respectively. In the cocktail formulations the conjugation of epirubicin with ofloxacin presents a more effective antibacterial activity with more than 3-fold reduction of ofloxacin concentration when comparing to the single ofloxacin system. By far, the most effective synergistic effect was obtained for the system where epirubicin was functionalized at nanoparticles surface (MNs@EPI), where a 40-fold and 33-fold reductions of ofloxacin concentration were obtained, in P. aeruginosa in comparison to the MNs-OFLO and MNs-EPI + OFLO systems, respectively. These effects are shown in all bacterial strains tested, even in strains that have acquired resistance mechanisms, such as MRSA.

2019-12-01·BMC Nutrition

Acceptability and utilization of a lipid-based nutrient supplement formulated for pregnant women in rural Niger: a multi-methods study

Article

作者: Grais, Rebecca F ; Kodish, Stephen R ; Isanaka, Sheila ; Zeilani, Mamane ; Guindo, Ousmane ; Mamaty, Abdoul Aziz

BACKGROUNDIn food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger.METHODSWe conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial.RESULTSParticipants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month.CONCLUSIONEpi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02145000. Registered 22 May 2014.

100 项与 FW-EPI 相关的药物交易

登录后查看更多信息