Isaac M. Adjei, Jahnelle Jordan, Nhan Tu, Thu Le Trinh, Wendy Kandell, Sheng Wei, Blanka Sharma
{"title":"Functional recovery of natural killer cell activity by nanoparticle-mediated delivery of transforming growth factor beta 2 small interfering RNA","authors":"Isaac M. Adjei, Jahnelle Jordan, Nhan Tu, Thu Le Trinh, Wendy Kandell, Sheng Wei, Blanka Sharma","doi":"10.1002/jin2.63","DOIUrl":"10.1002/jin2.63","url":null,"abstract":"<p>Natural killer (NK) cells are at the forefront of immunotherapies, as they have potent innate cytolytic effects on cancer cells. The success of NK cell therapies requires that they overcome immunosuppression in the tumor microenvironment. Tumors produce immunosuppressive factors like transforming growth factor beta (TGF-β) that inhibit the effector functions of NK cells. Silencing of TGF-beta signaling in NK cells is a potential approach to enhance their functions. However, transfection of NK cells by conventional methods is challenging. Here, we report the development of a nanoparticle (NP) system that delivers small interfering RNA for the TGF-β receptor 2 (TGFBR2) into NK cells to restore their activation against cancer cells. Manganese dioxide NPs were synthesized by the reduction of potassium permanganate by poly (allylamine), which effectively complexed siRNA and protected it from degradation. The NPs were cytocompatible with NK cells and, upon loading with TGFBR2 siRNA, resulted in a 90% knockdown of the TGFBR2 receptor. NP-mediated TGFBR2 receptor knockdown protected NK cells against TGF-β suppression, which was studied in both two-dimensional and three-dimensional lung cancer cell culture systems. Namely, NK cells treated with TGFBR2 siRNA loaded NPs demonstrated higher interferon gamma production, infiltration, and killing of lung cancer cells compared with control NK cells. This study demonstrates the feasibility of NP-mediated RNA interference in NK cells to increase their resilience to the immunosuppressive environments in solid tumors.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 4","pages":"98-112"},"PeriodicalIF":0.0,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43669952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel N. Nyamu, Lucy Ombaka, Eric Masika, Margaret Ng'ang'a
{"title":"One-pot microwave-assisted synthesis of size-dependent l-glutathione-capped spherical silver nanoparticles suitable for materials with antibacterial properties","authors":"Samuel N. Nyamu, Lucy Ombaka, Eric Masika, Margaret Ng'ang'a","doi":"10.1002/jin2.62","DOIUrl":"10.1002/jin2.62","url":null,"abstract":"<p>In the last years, there has been an alarming increase in antibiotic resistance by pathogenic microbes, which has become a major public health concern. There is a great interest in developing new antimicrobial for reducing the impact. Silver nanoparticles (AgNPs) as antibacterial agents are currently being studied to be used to fight these pathogenic microbes. The aim of the present study was to synthesize AgNPs of different sizes through the use of microwave and determine their antimicrobial activities. Synthesis of size-dependent <span>l</span>-glutathione-capped spherical nanoparticles through one-pot microwave synthesis was achieved, and their antimicrobial properties were determined. Different sizes of AgNPs between 5–10, 15–35, and 50–80 nm were made by varying the concentration of silver nitrate and using sodium borohydride (NaBH<sub>4</sub>) as a reducing agent. <span>l</span>-glutathione was used to stabilize the AgNPs to prevent them from aggregation in the colloidal solution. The synthesized AgNPs showed ultraviolet absorption at around 400 nm with high concentration of AgNO<sub>3</sub> having sharp peaks. The formed particles were crystalline in nature with uniform spherical shape. The formed AgNPs were of crystalline size of 9.94, 18.45, 34.96, 52.40, and 58.50 nm. Fourier transform infrared analysis confirmed conjugation of glutathione as a capping agent to AgNPs as the result of the formed spectra showing the absence of ─SH stretch. The high temperature generated by microwave helped to synthesize nanoparticles within a short time and by varying the concentration of AgNO<sub>3</sub> helped obtain the desired particle size. Glutathione conjugated well with AgNPs as a result of interaction of negative thiol resulting to colloidal stabilization and reduced aggregation. The antibacterial activity of AgNPs was found to be size dependent with the smaller size of 9.94 nm being more efficient than 18.45, 34.96, 52.40, and 58.50 nm against the tested strains <i>Bacillus subtilis</i> (ATCC 6633), <i>Escherichia coli</i> (ATCC 25922), <i>Salmonella</i> spp. (ATCC 700623), and <i>Staphylococcus aureus</i> (ATCC 25923). Of the four stains, <i>E. coli</i> was found to be the least affected by all three different particle sizes of the synthesized AgNPs.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 3","pages":"86-94"},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48505191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanomedicines towards targeting intracellular Mtb for the treatment of tuberculosis","authors":"Samantha Donnellan, Marco Giardiello","doi":"10.1002/jin2.61","DOIUrl":"10.1002/jin2.61","url":null,"abstract":"<p>Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), causes the most human deaths than any other diseases from a single infectious agent. Treatments are long and costly and have many associated side effects. Intracellular bacilli are slow growing and difficult to target, which is augmenting the emergence of multi-drug resistance. A hallmark trait of TB is the formation of granulomas, chronic cellular aggregates, which limit bacterial growth but provides a survival reservoir where bacilli may disseminate from. Targeting intracellular <i>Mtb</i> is challenging, but nanomedicine may offer a solution. Nanomedicine is a significantly growing research area and offers the potential for specific disease targeting, dosage reduction, and intracellular drug delivery. This review discusses the application of the various forms of nanomedicine towards targeting of <i>Mtb</i>.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 3","pages":"76-85"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.61","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44479831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intouch Sakpakdeejaroen, Sukrut Somani, Partha Laskar, Margaret Mullin, Christine Dufès
{"title":"Transferrin-bearing liposomes entrapping plumbagin for targeted cancer therapy","authors":"Intouch Sakpakdeejaroen, Sukrut Somani, Partha Laskar, Margaret Mullin, Christine Dufès","doi":"10.1002/jin2.56","DOIUrl":"10.1002/jin2.56","url":null,"abstract":"<p>The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination <i>in vivo</i>. We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin-targeted liposomes entrapping plumbagin and to evaluate their therapeutic efficacy <i>in vitro</i> and <i>in vivo</i>. The entrapment of plumbagin in transferrin-bearing liposomes led to an increase in plumbagin uptake by cancer cells and improved antiproliferative efficacy and apoptosis activity in B16-F10, A431, and T98G cell lines compared with that observed with the drug solution. <i>In vivo,</i> the intravenous injection of transferrin-bearing liposomes entrapping plumbagin led to tumour suppression for 10% of B16-F10 tumours and tumour regression for a further 10% of the tumours. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Transferrin-bearing liposomes entrapping plumbagin are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 2","pages":"54-71"},"PeriodicalIF":0.0,"publicationDate":"2019-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peri Korshed, Lin Li, Zhu Liu, Aleksandr Mironov, Tao Wang
{"title":"Size-dependent antibacterial activity for laser-generated silver nanoparticles","authors":"Peri Korshed, Lin Li, Zhu Liu, Aleksandr Mironov, Tao Wang","doi":"10.1002/jin2.54","DOIUrl":"10.1002/jin2.54","url":null,"abstract":"<p>Silver nanoparticles (Ag NPs) have been used widely for antibacterial applications; however, the effects of their sizes on antibacterial activities and toxicities to human cells, particularly for the laser-generated Ag NPs, are not fully understood. In this study, sucrose gradient centrifugation was used to separate laser-generated Ag NPs into different fractions by size. Transmission electron microscopy was used to analyze the size distribution of the Ag NPs, and well diffusion method was used to evaluate the antibacterial activity of the Ag NP fractions against the <i>Escherichia coli</i>. Results showed that the antibacterial effects of laser-generated Ag NPs inversely correlated to the particle size. Among Ag NP fractions with average sizes ranging 19–47 nm, the 19-nm Ag NPs presented the highest bactericidal effect. The smaller sized laser Ag NPs also significantly induced the generation of reactive oxygen species when applied to <i>E. coli</i>, compared with that of the larger sized laser Ag NPs. Cytotoxicity analysis revealed that the different sized laser-generated Ag NPs were not significantly toxic to the human fibroblasts and lung epithelial cells in a 72-h <i>in vitro</i> cell culture period. Understanding the size-dependent functional properties of the laser-generated Ag NPs helps informing the designs for future applications of the laser-generated Ag NPs.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 1","pages":"24-33"},"PeriodicalIF":0.0,"publicationDate":"2019-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.54","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45755995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Walid Mnasri, Lotfi Bentahar, Sophie Nowak, Olivier Sandre, Michel Boissière, Souad Ammar
{"title":"Evaluation of polyol-made Gd3+-substituted Co0.6Zn0.4Fe2O4 nanoparticles as high magnetization MRI negative contrast agents","authors":"Walid Mnasri, Lotfi Bentahar, Sophie Nowak, Olivier Sandre, Michel Boissière, Souad Ammar","doi":"10.1002/jin2.53","DOIUrl":"10.1002/jin2.53","url":null,"abstract":"<p>The structural, microstructural, and magnetic properties of ~5-nm-sized Co<sub>0.6</sub>Zn<sub>0.4</sub>Fe<sub>2 − <i>x</i></sub>Gd<sub><i>x</i></sub>O<sub>4</sub> nanoparticles were investigated in order to evaluate their capability to enhance the magnetic resonance imaging contrast as high magnetization agents. A focus was made on the solubility of Gd<sup>3+</sup> cations within the spinel lattice. By coupling X-ray diffraction to X-ray fluorescence spectroscopy, we demonstrated that only a limited fraction of Gd<sup>3+</sup> can substitute Fe<sup>3+</sup> ions into the whole crystal structure and does not exceed 6 at.-%. At this concentration, the room temperature (27°C) saturation magnetizations of the prepared superparamagnetic nanocrystals were found to be close to 80 emu g<sup>−1</sup>. Coating these nanoparticles with hydrophilic dopamine ligands leads to the formation of ~50-nm-sized clusters in water. As a consequence, relatively high <i>r</i><sub>2</sub>/<i>r</i><sub>1</sub> ratios of transverse to longitudinal proton relaxivities and high <i>r</i><sub>2</sub> values were measured in the resulting colloids at physiological temperature (37°C) for an applied magnetic field of 1.41 T: 33 and 188 mM<sup>−1</sup> sec<sup>−1</sup>, respectively, for the richest system in gadolinium. Moreover, after incubation with healthy human model cells (fibroblasts) at doses as high as 10 μg mL<sup>−1</sup>, they induce neither cellular death nor acute cellular damage making the engineered probes particularly valuable for negative magnetic resonance imaging contrasting.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"4 1","pages":"4-23"},"PeriodicalIF":0.0,"publicationDate":"2019-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.53","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42287672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmaceutical quality by design in academic nanomedicine research: stifling innovation or creativity through constraint?","authors":"Lea Ann Dailey","doi":"10.1002/jin2.52","DOIUrl":"10.1002/jin2.52","url":null,"abstract":"<p>Pharmaceutical quality by design (QbD) is a systematic approach to drug development that begins with predefined objectives and emphasises product and process understanding and control based on sound science and quality risk management. First and foremost, QbD is an experimental design philosophy, which emphasises the value of thorough intellectual planning prior to the commencement of laboratory studies. Academic researchers whose ambitions lie in translational science may benefit from the lessons learned by the pharmaceutical industry following implementation of QbD into their development philosophy. However, because of the very interdisciplinary nature of academic nanomedicine research, it is likely that very few investigators are aware of QbD and how aspects of it may be judiciously implemented in an academic research setting. This review provides an introduction to the main elements of QbD and gives examples of case studies where QbD has been applied to nanomedicine research.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 4","pages":"175-182"},"PeriodicalIF":0.0,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.52","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42671889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lai Jiang, Jia Lin, Clifford C. Taggart, José A. Bengoechea, Christopher J. Scott
{"title":"Nanodelivery strategies for the treatment of multidrug-resistant bacterial infections","authors":"Lai Jiang, Jia Lin, Clifford C. Taggart, José A. Bengoechea, Christopher J. Scott","doi":"10.1002/jin2.48","DOIUrl":"10.1002/jin2.48","url":null,"abstract":"<p>One of the most important health concerns in society is the development of nosocomial infections caused by multidrug-resistant pathogens. The purpose of this review is to discuss the issues in current antibiotic therapies and the ongoing progress of developing new strategies for the treatment of ESKAPE pathogen infections, which is acronymized for <i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and <i>Enterobacter</i> species. We not only examine the current issues caused by multidrug resistance but we also examine the barrier effects such as biofilm and intracellular localization exploited by these pathogens to avoid antibiotic exposure. Recent innovations in nanomedicine approaches and antibody antibiotic conjugates are reviewed as potential novel approaches for the treatment of bacterial infection, which ultimately may expand the useful life span of current antibiotics.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 3","pages":"111-121"},"PeriodicalIF":0.0,"publicationDate":"2018-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36689178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of the developmental neurotoxicity of silver nanoparticles and silver ions with mouse embryonic stem cells in vitro","authors":"Nuoya Yin, Bowen Hu, Renjun Yang, Shaojun Liang, Shengxian Liang, Francesco Faiola","doi":"10.1002/jin2.49","DOIUrl":"10.1002/jin2.49","url":null,"abstract":"<p>The wide applications of silver nanoparticles (AgNPs) have raised many concerns worldwide regarding their safety. The few previous studies on the developmental toxicity of AgNPs have been mostly dependent on animal experiments, which are time-consuming and costly. The rapid development of stem cell biology provides a new in vitro alternative to live animal assays for developmental toxicity studies. Here, we assessed the developmental neurotoxicity of AgNPs and Ag ions using a mouse embryonic stem cell (mESC) toxicology model. Our results showed that AgNP and Ag ion treatments did not affect mESC viability or cause accumulation of reactive oxygen species, at concentrations below 1 μg/mL. Conversely, AgNPs and Ag ions perturbed mESC global and neural progenitor cell-specific differentiation processes. In fact, both AgNPs and Ag ions induced the anomalous expression of neural ectoderm marker genes, such as <i>Sox1</i>, <i>Sox3</i>, <i>Map2</i>, <i>NeuroD</i>, <i>Nestin</i>, and <i>Pax6</i>, at concentrations lower than 0.1 μg/mL. Interestingly, AgNP effects manifested at earlier time points as compared with Ag ions. In addition, treatment with Ag ions generated neural progenitor cell abnormal morphology. Overall, our data proved that both AgNPs and Ag ions are toxicants, and their toxic effects are somehow different.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 3","pages":"133-145"},"PeriodicalIF":0.0,"publicationDate":"2018-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47078747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eliesmaziah Alias, Vijay Parikh, Araida Hidalgo-Bastida, Malcolm Wilkinson, Kelly S. Davidge, Tim Gibson, Duncan Sharp, Rameen Shakur, May Azzawi
{"title":"Doxorubicin-induced cardiomyocyte toxicity – protective effects of endothelial cells in a tri-culture model system","authors":"Eliesmaziah Alias, Vijay Parikh, Araida Hidalgo-Bastida, Malcolm Wilkinson, Kelly S. Davidge, Tim Gibson, Duncan Sharp, Rameen Shakur, May Azzawi","doi":"10.1002/jin2.42","DOIUrl":"10.1002/jin2.42","url":null,"abstract":"<p>Doxorubicin-induced cardiomyopathy is a clinically prevalent pathology, occurring as a sequelae following chemotherapy for cancer patients. In particular, the “first dose” effect has been particularly challenging, given the heterogeneous and multifactorial nature of this pathophysiology. Here, we describe the development of a physiologically relevant in vitro model for cardiotoxicity testing, using human cells. Primary cardiomyocytes, endothelial, and smooth muscle cells were tri-cultured in 2D, or within nano-fibrous scaffolds in a 3D environment, under dynamic nutrient flow, using the Quasi Vivo® system. State-of-the-art sensor chips were used to detect troponin I levels, 2 h after acute exposure to doxorubicin. We demonstrate a significant improvement in cardiomyocyte viability when grown in a 3D tri-culture environment over a 5-day period and a 10-fold reduction in doxorubicin-induced toxicity. Our tri-culture model can be used as a valuable tool for physiologically relevant assessment of drug-induced cardiotoxicity in vitro.</p>","PeriodicalId":91547,"journal":{"name":"Journal of interdisciplinary nanomedicine","volume":"3 3","pages":"122-132"},"PeriodicalIF":0.0,"publicationDate":"2018-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jin2.42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41865003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}