A novel low molecular weight nanocomposite hydrogel formulation for intra-tumoural delivery of anti-cancer drugs

Herein, an injectable formulation composed of a low molecular weight gelator (LMWG) based hydrogel and drug-loaded polymeric nanocapsules (NCs) is described. The NCs, made of hyaluronic acid and polyglutamic acid and loaded with C14-Gemcitabine (GEM C14), showed a size of 40 and 80 nm and a encapsulation efficiency > 90%. These NCs exhibited a capacity to control the release of the encapsulated drug for more than 1 month. GEM C14-loaded NCs showed activity against various cancer cell lines in vitro; cell growth inhibition by 50% (GI50) values of 15 ± 6, 10 ± 9, 13 ± 3 and 410 ± 463 nM were obtained in HCT 116, MIA PaCa-2, Panc-1 and Panc-1 GEM resistant cell lines respectively. Nanocomposite hydrogels were prepared using the LMWG - N4-octanoyl-2’-deoxycytidine and loaded for the first time with polymeric NCs. 2% and 4% w/v nanocapsule concentrations as compared to 8% w/v NC concentrations with 2 % and 3% w/v gelator concentrations gave mechanically stronger gels as determined by oscillatory rheology. Most importantly, the nanocomposite formulation reformed instantly into a gel after injection through a needle. Based on these properties, the nanocomposite gel formulation has potential for the intratumoural delivery of anticancer drugs

Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer Therapy

he O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI50 < 0.38 μM), targeting microtubule dynamics. By exploiting breast cancer cells’ upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, ∼120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt–JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDA-MB-231 cells than naked JAa (0.2 μM) treatment alone. Compared to naked JAa (0.2 μM), AFt–JAa achieves enhanced growth inhibition (2.5–14-fold; <0.02 μM < GI50 < 0.15 μM) in breast cancer cells; AFt–JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent (p < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)-polymerase, corroborate the augmented potency of AFt–JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors

Correction to “Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer Therapy”

Neil R. Thomas was added as an author. The change in authorship is reflected in the authorship of this Correction

Assessment of the Perception of Sustainability for Occupants of Residential Buildings: A Case Study in the UAE

The residential sector is multi-faceted by nature. Although evidence shows that the UAE is among the countries in the world that take sustainability seriously, there is a lack of information about the perception of sustainability by occupants in the residential sector in the UAE. The aim of this paper is to assess the perception of sustainability of the residential sector in the UAE, which is achieved by following a methodological framework using the relevant literature review and experts&rsquo; knowledge. An online survey was distributed to the targeted population, followed by a statistical analysis to fulfill the aim of the paper. Results confirm the correlation between social, economic, and environmental aspects of sustainability. Additionally, structural equation modeling reveals that the perception of sustainability is significantly influenced by economic and environmental aspects in the residential sector in the UAE. Comparative analysis shows a statistical difference in the perception of sustainability among gender, educational level, employment status, and monthly income. Finally, a predictive classification model is built to classify the perception of occupants based on their attributes using decision tree algorithms. The outcomes of this study would be beneficial to policy and decision makers, developers, contractors, designers, and facility management entities to enhance overall sustainability in the residential sector

An Apoferritin-Based Drug Delivery System for Jerantinine A Acetate for Breast Cancer Treatment

Natural products have been a major and critically important source of anti-cancer drugs and inspiration for drug discovery. The Aspidosperma alkaloid Jerantinine A (JA) is a natural compound that possesses potent antiproliferative activity against various human-derived carcinoma cell lines. Jerantinines elicit potent but unselective effects by inhibiting tubulin polymerisation, polo-like kinase 1 (PLK1) and increasing ROS levels in treated cancer cells. Herein, we address the poor cancer-selectivity of JA acetate (JAa) and by developing an apoferritin (AFt) delivery vehicle for JAa, which can target transferrin receptor-1 (TFR1)-overexpressing breast cancer cells. The therapeutic benefits of AFt-JAa were evaluated in a panel of breast carcinoma cell lines. By optimising the pH-mediated reassembly method, a high yield was achieved with ~77% protein recovery. Following optimisation, ~120 molecules of JAa were successfully encapsulated within the AFt protein cavity. The AFt-JAa formulation has comparable size, charge and cage-integrity to AFt stock, as demonstrated by dynamic light scattering (DLS) and native polyacrylamide gel electrophoresis (PAGE). AFt- JAa was stable for ≥ 10 months of storage at T = 4 ºC and pH 7.4. Treatment of cells with AFt-JAa significantly enhanced breast cancer cell growth inhibition in cells with high TFR1 expression but not MRC-5 fibroblasts that express low TFR1 levels; TFR1 levels were detected with western blot and flow cytometry. Enhanced selectivity of encapsulated JAa in TFR1-overexpressing breast cancer cells was explained by enhanced internalisation of 5-carboxyfluorescein-conjugated-human-AFt compared to TFR1-low expressing cells (MRC-5 fibroblasts). Consequently, enhanced AFt-JAa nanoformulation potency (over naked JAa) was attributed to greater intracellular accumulation of JAa in cells overexpressing TFR1 (SKBR-3, MDA-MB-231 and BT-474). Greater stability was observed for AFt-JAa in culture media under the treatment conditions (T = 37 ºC; ≤ 72 h) compared to the naked agent. The enhanced activity of AFt-JAa was supported by a greater reduction of colony formation in TFR1+ breast carcinoma cell lines SKBR-3, MDA-MB-468 and BT-474. Significantly lower number of viable cells, more profound cell cycle perturbation, including G2/M arrest, and increased apoptosis was evoked by AFt-JAa compared to JAa alone. Significant dose-dependent upregulation of biomarkers of apoptosis (cleaved PARP, decreased PLK1 and Mcl-1/Bcl-2 expression) further corroborates apoptosis. Treatment with naked and AFt-encapsulated JAa leads to the generation of ROS in MCF-7 and MDA-MB-231 cells, in addition to upregulating expression of WT p53 in MCF-7 cells, while repressing mutant p53 expression in both SKBR-3 and MDA-MB-231. These results indicate multiple cancer-related targets of JAa and confirm the natural product’s rich and diverse pharmacology. AFt alone exerts negligible effects on cell growth or survival as indicated from MTT, cell count, clonogenic, cell cycle analysis, annexin V apoptosis assays; neither does AFt impact the expression of apoptotic/antiapoptotic proteins, as shown by western blot. Thus, AFt is a potentially biocompatible nanocarrier for targeted delivery of JAa to minimise its toxicity and enhance its activity in TFR1-overexpressing tumours

An Apoferritin-Based Drug Delivery System for Jerantinine A Acetate for Breast Cancer Treatment

Natural products have been a major and critically important source of anti-cancer drugs and inspiration for drug discovery. The Aspidosperma alkaloid Jerantinine A (JA) is a natural compound that possesses potent antiproliferative activity against various human-derived carcinoma cell lines. Jerantinines elicit potent but unselective effects by inhibiting tubulin polymerisation, polo-like kinase 1 (PLK1) and increasing ROS levels in treated cancer cells. Herein, we address the poor cancer-selectivity of JA acetate (JAa) and by developing an apoferritin (AFt) delivery vehicle for JAa, which can target transferrin receptor-1 (TFR1)-overexpressing breast cancer cells. The therapeutic benefits of AFt-JAa were evaluated in a panel of breast carcinoma cell lines. By optimising the pH-mediated reassembly method, a high yield was achieved with ~77% protein recovery. Following optimisation, ~120 molecules of JAa were successfully encapsulated within the AFt protein cavity. The AFt-JAa formulation has comparable size, charge and cage-integrity to AFt stock, as demonstrated by dynamic light scattering (DLS) and native polyacrylamide gel electrophoresis (PAGE). AFt- JAa was stable for ≥ 10 months of storage at T = 4 ºC and pH 7.4. Treatment of cells with AFt-JAa significantly enhanced breast cancer cell growth inhibition in cells with high TFR1 expression but not MRC-5 fibroblasts that express low TFR1 levels; TFR1 levels were detected with western blot and flow cytometry. Enhanced selectivity of encapsulated JAa in TFR1-overexpressing breast cancer cells was explained by enhanced internalisation of 5-carboxyfluorescein-conjugated-human-AFt compared to TFR1-low expressing cells (MRC-5 fibroblasts). Consequently, enhanced AFt-JAa nanoformulation potency (over naked JAa) was attributed to greater intracellular accumulation of JAa in cells overexpressing TFR1 (SKBR-3, MDA-MB-231 and BT-474). Greater stability was observed for AFt-JAa in culture media under the treatment conditions (T = 37 ºC; ≤ 72 h) compared to the naked agent. The enhanced activity of AFt-JAa was supported by a greater reduction of colony formation in TFR1+ breast carcinoma cell lines SKBR-3, MDA-MB-468 and BT-474. Significantly lower number of viable cells, more profound cell cycle perturbation, including G2/M arrest, and increased apoptosis was evoked by AFt-JAa compared to JAa alone. Significant dose-dependent upregulation of biomarkers of apoptosis (cleaved PARP, decreased PLK1 and Mcl-1/Bcl-2 expression) further corroborates apoptosis. Treatment with naked and AFt-encapsulated JAa leads to the generation of ROS in MCF-7 and MDA-MB-231 cells, in addition to upregulating expression of WT p53 in MCF-7 cells, while repressing mutant p53 expression in both SKBR-3 and MDA-MB-231. These results indicate multiple cancer-related targets of JAa and confirm the natural product’s rich and diverse pharmacology. AFt alone exerts negligible effects on cell growth or survival as indicated from MTT, cell count, clonogenic, cell cycle analysis, annexin V apoptosis assays; neither does AFt impact the expression of apoptotic/antiapoptotic proteins, as shown by western blot. Thus, AFt is a potentially biocompatible nanocarrier for targeted delivery of JAa to minimise its toxicity and enhance its activity in TFR1-overexpressing tumours

Environmental and Economic Impact Assessments of a Photovoltaic Rooftop System in the United Arab Emirates

The shift toward renewable energy resources, and photovoltaic systems specifically, has gained a huge focus in the past two decades. This study aimed to assess several environmental and economic impacts of a photovoltaic system that installed on the rooftop of an industrial facility in Dubai, United Arab Emirates (UAE). The life cycle assessment method was employed to study all the flows and evaluate the environmental impacts, while several economic indicators were calculated to assess the feasibility and profitability of this photovoltaic system. The results showed that the production processes contributed the most to the environmental impacts, where the total primary energy demand was 1152 MWh for the whole photovoltaic system, the total global warming potential was 6.83 × 10–2 kg CO2-eq, the energy payback time was 2.15 years, the carbon dioxide payback time was 1.87 years, the acidification potential was 2.87 × 10–4 kg SO2-eq, eutrophication potential was 2.45 × 10–5 kg PO43-eq, the ozone layer depletion potential was 4.685 × 10–9 kgCFC-11-eq, the photochemical ozone creation potential was 3.81 × 10–5 kg C2H4-eq, and the human toxicity potential was 2.38 × 10–2 kg1,4-DB-eq for the defined function unit of the photovoltaic system, while the economic impact indicators for the whole system resulted in a 3.5 year payback period, the benefit to cost ratio of 11.8, and 0.142 AED/kWh levelized cost of electricity. This was the first study to comprehensively consider all of these impact indicators together. These findings are beneficial inputs for policy- and decision-makers, photovoltaic panel manufacturers, and photovoltaic contractors to enhance the sustainability of their processes and improve the environment

Assessment of the Perception of Sustainability for Occupants of Residential Buildings: A Case Study in the UAE

The residential sector is multi-faceted by nature. Although evidence shows that the UAE is among the countries in the world that take sustainability seriously, there is a lack of information about the perception of sustainability by occupants in the residential sector in the UAE. The aim of this paper is to assess the perception of sustainability of the residential sector in the UAE, which is achieved by following a methodological framework using the relevant literature review and experts’ knowledge. An online survey was distributed to the targeted population, followed by a statistical analysis to fulfill the aim of the paper. Results confirm the correlation between social, economic, and environmental aspects of sustainability. Additionally, structural equation modeling reveals that the perception of sustainability is significantly influenced by economic and environmental aspects in the residential sector in the UAE. Comparative analysis shows a statistical difference in the perception of sustainability among gender, educational level, employment status, and monthly income. Finally, a predictive classification model is built to classify the perception of occupants based on their attributes using decision tree algorithms. The outcomes of this study would be beneficial to policy and decision makers, developers, contractors, designers, and facility management entities to enhance overall sustainability in the residential sector