Efficient Delivery Research Articles

Mitochondria-targeted nanoparticles based on glycated oat protein for enhanced curcumin bioavailability and antioxidant activity

Curcumin is a hydrophobic dietary supplement and can mitigate oxidative damage. However, the low bioavailability of curcumin impedes its application in functional foods. Protein-coated nanoparticles are susceptible to environmental stress and have limited ability to reach mitochondria, where reactive oxygen species are generated. To overcome this limitation, we prepared mitochondria-targeted nanoparticles by modifying glycosylated oat protein isolate with triphenylphosphonium bromide for the efficient delivery of curcumin. In this study, the curcumin was incorporated into the spherical nanoparticles with high entrapment efficiency and loading capacity. The nanoparticles increased the stability of curcumin during heat treatment and light irradiation. The bioavailability of curcumin was improved in the nanoparticles due to their strong resistance against in vitro gastric digestion and good permeability across the Caco-2 cell monolayer. The nanoparticles realized lysosomal escape and exhibited specific accumulation in mitochondria upon internalization by Caco-2 cells. The mitochondria-targeted nanoparticles with no cytotoxicity further enhanced the antioxidant activity of curcumin by preserving mitochondrial membrane potential, increasing antioxidant enzyme activities, decreasing the concentrations of intracellular reactive oxygen species and malondialdehyde. This study highlights the potential application of glycosylated proteins in developing nanocarriers for precise delivery of hydrophobic nutrients.

A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses.

Bacterium-like particles (BLP) are the peptidoglycan skeleton particles of lactic acid bacteria, which have high safety, mucosal delivery efficiency, and adjuvant effect. It has been widely used in recent years in the development of vaccines. Existing anchoring proteins for BLP surfaces are few in number, so screening and characterization of new anchoring proteins are necessary. In this research, we created the OACD (C-terminal domain of Escherichia coli outer membrane protein A) to serve as an anchoring protein on the surface of BLP produced by the immunomodulatory bacteria Levilactobacillus brevis 23017. We used red fluorescent protein (RFP) to demonstrate the novel surface display system's effectiveness, stability, and ability to be adapted to a wide range of lactic acid bacteria. Furthermore, this study employed this surface display method to develop a novel vaccine (called COB17) by using the multi-epitope antigen of Clostridium perfringens as the model antigen. The vaccine can induce more than 50% protection rate against C. perfringens type A challenge in mice immunized with a single dose and has been tested through three routes. The vaccine yields protection rates of 75% for subcutaneous, 50% for intranasal, and 75% for oral immunization. Additionally, it elicits a strong mucosal immune response, markedly increasing levels of specific IgG, high-affinity IgG, specific IgA, and SIgA antibodies. Additionally, we used protein anchors (PA) and OACD simultaneous to show several antigens on the BLP surface. The discovery of novel BLP anchoring proteins may expand the possibilities for creating mucosal immunity subunit vaccines. Additionally, it may work in concert with PA to provide concepts for the creation of multivalent or multiple vaccines that may be used in clinical practice to treat complex illnesses.

Optimization of hybrid delivery by vehicle and drones

In this paper, we introduce the optimization of hybrid delivery by vehicle and drones. Hybrid delivery by vehicle and drones is advantageous for improving O2O last-mile delivery efficiency. However, vehicle stop selection and drone delivery sortie arrangement are challenging in the optimization of hybrid delivery by vehicle and drones because cyclic sorties and forward sorties jointly influence the total makespan of the delivery. To minimize the delivery makespan, an MILP model for hybrid delivery is formulated considering both the cyclic sorties and forward sorties of drones. In the proposed model, the intertwined influences of the flight times of cyclic and forward sorties and their further effects on total delivery makespan are depicted. Additionally, we introduce an ACO based on set covering for the selection of vehicle stops and a customized HGSADC for the arrangement of drone sorties. A study based on a simulated case and experiments based on 40 generated instances at different scales are explored to assess the optimization of hybrid delivery by vehicle and drones.

A machine learning-based approach to predict energy layer for each field in spot-scanning proton arc therapy for lung cancer: A feasibility study.

Determining the optimal energy layer (EL) for each field, under considering both dose constraints and delivery efficiency, is crucial to promoting the development of proton arc therapy (PAT) technology. This study aimed to explore the feasibility and potential clinical benefits of utilizing machine learning (ML) technique to automatically select EL for each field in PAT plans of lung cancer. Proton Bragg peak position (BPP) was employed to characterize EL. The ground truth BPPs for each field were determined using the modified ELO-SPAT framework. Features in geometric, water-equivalent thicknesses (WET) and beamlet were defined and extracted. By analyzing the relationship between the extracted features and ground truth, a polynomial regression model with L2-norm regularization (Ridge regression) was constructed and trained. The performance of the regression model was reported as an error between the predictions and the ground truth. Besides, the predictions were used to make PAT plans (PAT_PRED). These plans were compared with those using the ground truth BPPs (PAT_TRUTH) and the mid-WET of the target volumes (PAT_MID) in terms of relative biological effectiveness-weighted dose (RWD) distributions. One hundred ten patients with lung cancer, a total of 7920 samples, were enrolled retrospectively, with 5940 cases randomly selected as the training set and the remaining 1980 cases as the testing set. Nine patients (648 samples) were collected additionally to evaluate the regression model in terms of plan quality and robustness. With regard to the prediction errors, the root mean squared errors and mean absolute errors between the ML-predicted and ground truth BPPs for the testing set were 9.165 and 6.572mm, respectively, indicating differences of approximately two to three ELs. As for plan quality, the PAT_TRUTH and PAT_PRED plans performed similarly in terms of plan robustness, target coverage and organs at risk (OARs) protection, with differences smaller than 0.5Gy(RBE). This trend was also observed for dose conformity and uniformity. The PAT_MID plans produced the lowest robustness index and lowest doses to OARs, along with the highest heterogeneity index, indicating better protection for OARs, improved plan robustness, but compromised dose homogeneity. Additionally, for relatively small tumor sizes, the PAT_MID plan demonstrated a notably poor dose conformity index. Within this cohort under investigation, our study demonstrated the feasibility of using ML technique to predict ELs for each field, offering a fast (within 2 s) and memory-efficient reduced way to select ELs for PAT plan.

Ferritin nanocage-enabled detection of pathological tau in living human retinal cells

Tauopathies, including Alzheimer’s disease and Frontotemporal Dementia, are debilitating neurodegenerative disorders marked by cognitive decline. Despite extensive research, achieving effective treatments and significant symptom management remains challenging. Accurate diagnosis is crucial for developing effective therapeutic strategies, with hyperphosphorylated protein units and tau oligomers serving as reliable biomarkers for these conditions. This study introduces a novel approach using nanotechnology to enhance the diagnostic process for tauopathies. We developed humanized ferritin nanocages, a novel nanoscale delivery system, designed to encapsulate and transport a tau-specific fluorophore, BT1, into human retinal cells for detecting neurofibrillary tangles in retinal tissue, a key marker of tauopathies. The delivery of BT1 into living cells was successfully achieved through these nanocages, demonstrating efficient encapsulation and delivery into retinal cells derived from human induced pluripotent stem cells. Our experiments confirmed the colocalization of BT1 with pathological forms of tau in living retinal cells, highlighting the method’s potential in identifying tauopathies. Using ferritin nanocages for BT1 delivery represents a significant contribution to nanobiotechnology, particularly in neurodegenerative disease diagnostics. This method offers a promising tool for the early detection of tau tangles in retinal tissue, with significant implications for improving the diagnosis and management of tauopathies. This study exemplifies the integration of nanotechnology with biomedical science, expanding the frontiers of nanomedicine and diagnostic techniques.

The effect of employees’ health benefits on the performance of commercial state corporations in Kenya

This study sought to assess the effect of employees’ health benefits on the performance of Commercial State Corporations in Kenya. Commercial state corporations are established by the government to offer efficient and effective citizen service delivery whilst surrendering back investment income at the end of each financial year. Despite this, most of them have performed dismally over the years, questioning their justification for continued existence. A survey research design was used to conduct this study, targeting 612 managers of various cadres in the 68 commercial state corporations in Kenya. The Yamane sampling formula was used to arrive at a sample size of 242 managers in these corporations. Data collected through structured questionnaires was analysed using both inferential and descriptive statistics. Multiple regression models and Hierarchical regression were used to test hypotheses for moderation. The outcomes of the hierarchical regression model on all the variables revealed that employees' health benefits (β= 0.138, p= 0.000, p<0.05) had a significant positive relationship with the performance of commercial state corporations. These findings contribute novel insights into the influence of employee compensation on the performance of commercial state corporations. The study concluded that employee compensation affects the performance of commercial state corporations and that remuneration policy guidelines strengthen the positive linkage between employee compensation and performance outcomes. The study recommended that commercial state corporations should give higher priority to employee’s health benefits and Remuneration policy guidelines as they are crucial in enhancing their performance.

Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs

BackgroundTransdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity.ResultsWe fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility.ConclusionsThe present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

Energy efficient data dissemination in wireless sensor network enabled IoT using domain‐adaptive message passing graph neural network

SummaryIn the past few years, restricted wireless sensor networks (WSNs) enabled the Internet of Things (IoT) have attracted significant attention and expansion to enhance service delivery and resource efficiency. Dissemination is a service offered by WSN that uses radio transmission and over‐the‐air programming for updating the deployed sensor nodes through online. The centralized data dissemination methods are replaced by the distributed approaches because they affect the drawbacks of a single point of failure, no scalability, and insecurity. Therefore, an Energy Efficient Protocol for Data Dissemination in Wireless Sensor network‐enabled IoT using Domain‐Adaptive Message Passing Graph Neural Network (EEP‐WSN‐IoT‐DMPGNN) is proposed in this paper. The nodes are formed as clusters utilizing the Deep Fuzzy Curriculum Clustering (DFCC) technique that rewards nodes belonging to a given cluster. By using the Crayfish Optimization Algorithm (COA), the Cluster Head (CH) selection optimally chose the ideal CH and satisfies the multiple objective functions, such as energy, delay, traffic density, and distance. Afterward, domain‐adaptive Message Passing Graph Neural Network (DMPGNN) based routing protocol is developed, the input given to the routing protocol includes a sink, action history, future node, and maximum‐distance node, which attains enhanced data transfer in the chosen path. The proposed technique attains a lower no. of dead nodes, lower energy consumption, and higher Network Lifetime while analyzed with existing techniques, such as routing technique depending on deep learning for effectual data transmission in 5G WSN communication (DL‐RPDT‐WSN), Reinforcement‐Learning base energy effectual optimized routing protocol in WSN (RL‐EERP‐WSN), and Energy‐efficient intellectual routing method for IoT‐enabled WSN (EIR‐IoT‐WSN), respectively.

Towards eco-friendly plant growth regulator: A robustly stable and efficient uniconazole emulsion based on onion-like lamellar liquid crystal

As a commonly water-based pesticide formulation, conventional Emulsions in Water (EWs) always suffer from demulsification in actual complex environments and burst release due to their thermodynamic instability. The ecotoxicity and phytotoxicity caused by chemosynthetic adjuvants cannot be ignored. To address these issues, herein, using a soybean lecithin-based lamellar liquid crystal emulsion (LCE) as the carrier, we construct a robustly stable and low-toxicity EW with the “onion-like” bionic structure and achieve the efficient delivery of plant growth regulator (PGR) uniconazole (UZ). The hydrophobic UZ is firmly encapsulated within the orderly assembled Oil-in-Liquid Crystal-in-Water (O/LC/W) multilayers. This confinement endows UZ-LCE with robust stability, even while encountering disturbances such as dilution, shaking, and changes in pH, ions, and temperature. Furthermore, UZ-LCE exhibits enhanced wettability and affinity to foliar surfaces, as well as specific sustained-release ability. Owing to these superiorities of UZ-LCE, during two consecutive years of efficacy evaluations in cotton field experiments, UZ-LCEs administered through drip irrigation and foliar spray demonstrate remarkable enhancements in controlling excessive plant growth, increasing chlorophyll content, and boosting flower bud formation, surpassing the effectiveness of conventional EWs. UZ-LCE even outperforms commercial preparations (WP and SC) in balancing vegetative growth and reproductive growth, resulting in an 8.3% increase in yield. This research provides an innovative pesticide formulation with eco-friendly adjuvants, less organic solvent, and synergistic functionalities, which is prospective to be extended to other pesticide EWs and contribute to sustainable agriculture.

A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.

New Generation Nebulizers.

Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as breath-enhanced and breath-triggered devices have improved delivery efficiency and ease of use, yet are still suitable for delivery of nebulized medications approved in this category. However, recent developments of vibrating membrane or mesh nebulizers have given rise to a significant increase in delivery efficiency requiring reformulation of former drug products or development of new formulations to match the enhanced delivery characteristics of these new devices. In addition, the electronic nature of the new devices enables tailoring to specific applications and patient groups, such as guiding or facilitating optimal breathing and improving adherence to the therapeutic regimen. Addressing these patient needs leads to new nebulization technologies being embedded in devices with fundamentally distinct functionality, modes of operation and patient interfaces. Therefore, new generation nebulizers can no longer be regarded as one category with fairly similar performance characteristics but must be clinically tested and approved as drug/device combinations together with the specific drug formulation, similar to the approval of pressurized metered-dose inhalers and dry powder inhalers. From a regulatory viewpoint, it is required that drug and device are associated with each other as combinations by clear, mutually conforming labels or, even more desirably, by distinct container-closure systems (closed system nebulizer).

Assessing the expectations of Generation Z customers towards last-mile delivery in E-commerce: A case study in Ho Chi Minh City

This study focuses on assessing the impact of various factors influencing Generation Z consumers' expectations of last-mile delivery services when purchasing goods on e-commerce platforms within Ho Chi Minh City (HCMC), to improve service quality and propose delivery processes for efficient last-mile delivery. What is new compared to previous studies is the emphasis on the impact of environmental protection policies and green initiatives on the expectations of Gen Z customers. In this study, the authors propose the factor "Environmental Protection Policy" to build a scale to measure customer expectations in last-mile delivery service. A survey involving 435 participants who belong to Gen Z and frequently utilize e-commerce services in HCMC provided the primary data for this analysis. Utilizing quantitative analytical techniques, including Cronbach's alpha reliability test, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and multiple regression analysis, this research tested several hypotheses. The results corroborate that the expectations of Gen Z consumers regarding delivery services on e-commerce platforms in HCMC are significantly shaped by five pivotal factors: Delivery speed, reliability, responsiveness, environmental protection policy, and cost. The study notably highlights cost as the predominant factor exerting the most substantial influence on the expectations concerning last-mile delivery services. This study has made a significant contribution to the body of knowledge that e-commerce platforms and logistics firms may use to raise the bar for delivery services that Gen Z consumers anticipate.

Lipid-Based Nanocarriers for Targeted Gene Delivery in Lung Cancer Therapy: Exploring a Novel Therapeutic Paradigm.

Lung cancer is a significant cause of cancer-related death worldwide. It can be broadly categorised into small-cell lung cancer (SCLC) and Non-small cell lung cancer (NSCLC). Surgical intervention, radiation therapy, and the administration of chemotherapeutic medications are among the current treatment modalities. However, the application of chemotherapy may be limited in more advanced stages of metastasis due to the potential for adverse effects and a lack of cell selectivity. Although small-molecule anticancer treatments have demonstrated effectiveness, they still face several challenges. The challenges at hand in this context comprise insufficient solubility in water, limited bioavailability at specific sites, adverse effects, and the requirement for epidermal growth factor receptor inhibitors that are genetically tailored. Bio-macromolecular drugs, including small interfering RNA (siRNA) and messenger RNA (mRNA), are susceptible to degradation when exposed to the bodily fluids of humans, which can reduce stability and concentration. In this context, nanoscale delivery technologies are utilised. These agents offer encouraging prospects for the preservation and regulation of pharmaceutical substances, in addition to improving the solubility and stability of medications. Nanocarrier-based systems possess the notable advantage of facilitating accurate and sustained drug release, as opposed to traditional systemic methodologies. The primary focus of scientific investigation has been to augment the therapeutic efficacy of nanoparticles composed of lipids. Numerous nanoscale drug delivery techniques have been implemented to treat various respiratory ailments, such as lung cancer. These technologies have exhibited the potential to mitigate the limitations associated with conventional therapy. As an illustration, applying nanocarriers may enhance the solubility of small-molecule anticancer drugs and prevent the degradation of bio-macromolecular drugs. Furthermore, these devices can administer medications in a controlled and extended fashion, thereby augmenting the therapeutic intervention's effectiveness and reducing adverse reactions. However, despite these promising results, challenges remain that must be addressed. Multiple factors necessitate consideration when contemplating the application of nanoparticles in medical interventions. To begin with, the advancement of more efficient delivery methods is imperative. In addition, a comprehensive investigation into the potential toxicity of nanoparticles is required. Finally, additional research is needed to comprehend these treatments' enduring ramifications. Despite these challenges, the field of nanomedicine demonstrates considerable promise in enhancing the therapy of lung cancer and other respiratory diseases.

Carrier‐Free Disulfiram Based Nanomedicine for Enhanced Cancer Therapy

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs. However, the carrier materials and intricate nature of multifunctional design always hindered the clinical transformation of nanomedicines. Herein, a novel carrier‐free anticancer nanomedicine (CFDC) with tailored morphologies including nanodots, nanorod and nanosheet were prepared using the clinically approved anti‐alcoholism drug disulfiram (DSF) via supramolecular assembly process. Our study reveals that CFDC induces the production of reactive oxygen species and activates the downstream apoptosis‐related c‐Jun N‐terminal kinase (JNK) and p‐38 pathway. In addition, the CFDC effectively counteract the inhibitory effect of NF‐κB expression on ROS‐induced cellular cytotoxicity, ultimately resulting in enhanced cell apoptosis, which is not achievable by pure DSF and the simply mixing of DSF and Cu2+ (DSF + Cu). Notably, the CFDC exhibits 3.1‐, 3.0‐ folds increased on cancer cell DNA damage compared with the DSF, and DSF + Cu groups. In vivo experiments conducted on breast‐ or prostate‐bearing mice modals demonstrated that the CFDC exhibits a higher efficacy in suppressing the tumor growth. The remarkable drug delivery efficiency and better anticancer effect of CFDC nanodrug provide promising prospects for the clinical transformation of DSF based nanodrug in cancer therapy.

An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo

The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.

Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues.

Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example of the leap in the development of mRNA technologies was the mass vaccination against COVID-19 during the pandemic. The emergence of large-scale technology and positive experience of mRNA immunization sparked the development of antiviral and anti-cancer mRNA vaccines as well as therapeutic mRNA agents for genetic and other diseases. To facilitate mRNA delivery, lipid nanoparticles (LNPs) have been successfully employed. However, the diverse use of mRNA therapeutic approaches requires the development of adaptable LNP delivery systems that can control the kinetics of mRNA uptake and expression in target cells. Here, we report effective mRNA delivery into cultured mammalian cells (HEK293T, HeLa, DC2.4) and living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or the newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) cationic lipids. Using end-point and real-time monitoring of Fluc mRNA expression, we showed that these LNPs exhibited an unusually delayed (of over 10 h in the case of the 2X7-based system) but had highly efficient and prolonged reporter activity in cells. Accordingly, both LNP formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided efficient luciferase production in mice, peaking on day 3 after intramuscular injection. Notably, the bioluminescence was observed only at the site of injection in caudal thigh muscles, thereby demonstrating local expression of the model gene of interest. The developed mRNA delivery systems hold promise for prophylactic applications, where sustained synthesis of defensive proteins is required, and open doors to new possibilities in mRNA-based therapies.

Methotrexate-loaded Fe-metal organic frameworks: Synthesis, characterizations, and drug release investigations

Efficient diagnoses and effective treatment of diseases like cancer can be achieved by designing and developing targeted and controlled drug delivery systems. Metal-organic frameworks (MOFs) are promising drug delivery systems due to large surface area, tunable pore sizes, and controlled drug release. Herein, we report the loading and release of methotrexate (MTX) in MIL-101-Fe MOF as a drug delivery system. The functional groups, crystal structure, and morphology of the as-synthesized MOF was determined by Fourier transform infrared spectroscopy (FTIR), powdered X-ray diffraction and scanning electron microscopy (SEM), respectively. Interestingly, the MOF exhibited 84 % encapsulation efficiency for MTX and 62 % release in the initial 50 h at pH 5.5, which is ideal for tumor tissue. The MTX@MIL-101-Fe effectively killed the HeLa cells from human cervical cancer. Particularly noteworthy was that neither MIL-101-Fe nor MTX@MIL-101-Fe showed toxicity to healthy Vero cells. It proves that the Methotrexate was released from MTX@MIL-101-Fe in cancer cells at pH 5.5 and caused apoptosis. Theoretical studies used density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to explore three possible Methotrexate-MIL-101-Fe encapsulation complexes. The complex with the drug attached at the carboxylate-bridge site showed the highest binding. Moreover, a decrease in the calculated band gap was also observed during the encapsulation process. This study suggests that MIL-101-Fe can be a promising candidate for target-specific and efficient delivery of Methotrexate to cancer cells with reduced side effects.

Stimuli-Responsive Aptamer-Drug Conjugates for Targeted Drug Delivery and Controlled Drug Release.

Chemotherapy has been widely used for cancer therapy but with unsatisfied efficacy, mainly due to the inefficient delivery of anticancer agents. Among the critical "five steps" drug delivery process, internalization into tumor cells and intracellular drug release are two important steps for the overall therapeutic efficiency. Strategy based on active targeting or TME-responsive has been developed individually to improve therapeutic efficiency, but with limited improvement. However, the combination of these two strategies could potentially augment the drug delivery efficiency and therapeutic efficiency, consequently. Therefore, we constructed a library of stimuli-responsive aptamer-drug conjugates (srApDCs), as "dual-targeted" strategy for cancer treatment that enables targeted drug delivery and controlled drug release. Specifically, we used different stimuli-responsive linkers to conjugate a tumor-targeting aptamer (i.e., AS1411) with drugs, forming the library of srApDCs for targeted cancer treatment. Our design hypothesis was validated by the experimental data, which indicated that the aptamer could selectively enhance uptake of the srApDCs and the linkers could be cleaved by pathological cues in the TME to release the drug payload, leading to a significant enhancement of therapeutic efficacy. These results underscore the potential of our approach, providing a promising methodology for cancer therapy. This article is protected by copyright. All rights reserved.

Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.

Mathematical Model and Statistical Assessment of Non Linear Scheduling Optimization in Cloud Environment using Improved Cuckoo Search Algorithm

The scheduling optimization subject is indeed one of the most effective solutions in cloud system area to ensure the high systems performance and resource usage. The novelty presented in this study is a mathematical model that draws on an Improved Cuckoo Search Algorithm as a scheduling non-linear optimizer for the cloud computing environment. The model under consideration takes into account the underlying complications as well as the varying nature of the use of cloud resources, primarily addressing the latency issue with priority given to the increase of the throughput. Improved Cuckoo Search (ICS) Algorithm, developed on 'cuckoo search' algorithm, uses adaptive step size and probabilistic switching, which, in turn, ensure that the solution space is both being properly examined and exploited. The applications’ utilization of the scheduling mathematical model is based on an elaborately designed theoretical background representing the task as a non-linear optimization problem that meets all the specific constraints and objectives important in cloud computing. Statistical reassessment involves the comparison of the proposed model with standard benchmarks. The proposed model superiority is evident in terms of convergence speed, solution quality and robustness against diverse workloads, as shown in varied tests. The findings of this research contributes to the field by deriving a specialized tool commonly used by the cloud service provider in designing resource scheduling, enhancing the service delivery and operational efficiency.