Nanoparticle-based Approaches Research Articles

Nanodrug delivery systems for metabolic chronic liver diseases: advances and perspectives.

Nanomedicines are revolutionizing healthcare as recently demonstrated by the Pfizer/BioNTech and Moderna COVID-2019 vaccines, with billions of doses administered worldwide in a safe manner. Nonalcoholic fatty liver disease is the most common noncommunicable chronic liver disease, posing a major growing challenge to global public health. However, due to unmet diagnostic and therapeutic needs, there is great interest in the development of novel translational approaches. Nanoparticle-based approaches offer novel opportunities for efficient and specific drug delivery to liver cells, as a step toward precision medicines. In this review, the authors highlight recent advances in nanomedicines for the generation of novel diagnostic and therapeutic tools for nonalcoholic fatty liver disease and related liver diseases.

Inorganic Nanoparticles-Based Systems in Biomedical Applications of Stem Cells: Opportunities and Challenges.

Stem cells (SC) are a kind of cells with self renewing ability and multipotent differentiation, which can differentiate into many types of cells such as osteoblast, chondrocyte, neurocyte to treat disease like osteoporosis, osteoarthritis and Alzheimer's disease. Despite the development of novel methods for inducing cell differentiation, the inefficiency and complexity of controlling differentiation of stem cells remain a serious challenge, which necessary to develop a new and alternative approach for effectively controlling the direction of stem cell differentiation in vitro and in vivo in stem cells therapy. Recent advancement in nanotechnology for developing a new class of inorganic nanoparticles that exhibit unique chemical and physical properties holds promise for the treatment of stem cells. Over the last decade, inorganic nanoparticle-based approaches against stem cells have been directed toward developing nanoparticles with drug delivery, or utilizing nanoparticles for controlled cell behaviors, and applying nanoparticles for inducing cell differentiation directly. In addition, a strategy to functionalize inorganic nanoparticles as a nanoprobe towards enhanced penetration through near-infrared light or nuclear magnetic resonance has been receiving considerable interest by means of long-term tracking stem cell in vivo. This review summarizes and highlights the recent development of these inorganic nanoparticle-based approaches as potential therapeutics for controlling differentiation of stem cells and so on for stem cell therapy, along with current opportunities and challenges that need to be overcome for their successful clinical translation.

A scientometrics study of the nanomedicines assisted in respiratory diseases.

Nanomedicine has been extensively studied for its versatility and broad-spectrum applications of theranostics in the research of respiratory disease. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on nanomedicine applied in the research of respiratory disease has not been reported so far, which would be of major importance to relevant researchers. To explore and exhibit the research status and developing trend of nanomedicines deployed in basic or clinical research in respiratory disease, the research ecosystem and exciting subareas were profiled based on the massive data mining and visualization from the relevant works reported from 2006 to 2021. Data were collected from the Web of Science database. Data statistics software and bibliometric analysis software were employed to visualize the research trend and the relationship between respiratory diseases and nanomedicines in each representative direction. The cluster analysis and burst detections indicated that the improvement of drug delivery and vaccine developments are the up-to-date key directions in nanomedicines for respiratory disease research and treatments. Furthermore, we emphatically studied four branch areas in this field including COVID-19, nanotube, respiratory syncytial virus, and mRNA vaccine those are selected for in-depth mining and bibliometric coupling analysis. Research trends signify the future focuses will center on preventing respiratory diseases with mRNA vaccines using nanoparticle-based approaches. We anticipate our study will enable researchers to have the panorama and deep insights in this area, thus inspiriting further exploitations especially the nanobiomaterial-based systems for theranostic applications in respiratory disease treatment.

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011–2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1–3 trials.

Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion.

Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal β-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including virus-like particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in Escherichia coli and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the β-barrel from fHbp, including ferritin, a de novo designed aldolase from Thermotoga maritima, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structure-based design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens.

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage.

The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient's adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models.

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

Abstract: Efficient delivery of therapeutic material to target site of the inner ear is considered as the most challenging process due to their poor blood flow and inaccessibility sensitivity towards chemical stimuli, inability of drug to be delivered as well. Novel nanoparticlebased drug transport approaches have emerged for overcoming the restriction associated with inner ear therapeutic material delivery. The main focus of this article is to highlight the potential benefits, pre-clinical level otoprotective effect of different types of NPs based payload delivery strategies in mitigating sensorineural hearing impairment resulting from medication (cisplatin and antibiotic treatment) and noise exposure. This review converses about advantage of nanocarrier assisted targeted cell specific inner ear drug delivery approach and demonstrates that targeted NPs delivery systems have the capability to be utilized as vehicle to transport therapeutic materials into the OHCs within the cochlea in controlled and sustained way and maximize following therapeutic effects. Efficacy of systemic and minimally invasive intratympanic and RWM approach for delivering steroids/ genetic material to the inner ear has also been compared in this article. Understanding the importance (design, formulation, cochlear biocompatibility and cell specific binding efficiency of NPs, mechanistic pathways, route of delivery, positive therapeutic outcomes) and hitches (adverse effects after treatment, negative therapeutic outcome) of currently available NPs based drug delivery systems offer new opportunity to develop best treatment methods for sensorineural hearing dysfunction. Keywords: Nanocarriers, Otoprotective agents, Sensorineural heating loss, Ototoxicity, Noise trauma, Ototoxin.

Nanoparticle-based immunotherapy of pancreatic cancer.

Pancreatic cancer (PC) has a complex and unique tumor microenvironment (TME). Due to the physical barrier formed by the desmoplastic stroma, the delivery of drugs to the tumor tissue is limited. The TME also contributes to resistance to various immunotherapies such as cancer vaccines, chimeric antigen receptor T cell therapy and immune checkpoint inhibitors. Overcoming and/or modulating the TME is therefore one of the greatest challenges in developing new therapeutic strategies for PC. Nanoparticles have been successfully used as drug carriers and delivery systems in cancer therapy. Recent experimental and engineering developments in nanotechnology have resulted in increased drug delivery and improved immunotherapy for PC. In this review we discuss and analyze the current nanoparticle-based immunotherapy approaches that are at the verge of clinical application. Particularly, we focus on nanoparticle-based delivery systems that improve the effectiveness of PC immunotherapy. We also highlight current clinical research that will help to develop new therapeutic strategies for PC and especially targeted immunotherapies based on immune checkpoint inhibitors.

Combining Radiotherapy (RT) and Photodynamic Therapy (PDT): Clinical Studies on Conventional RT-PDT Approaches and Novel Nanoparticle-Based RT-PDT Approaches under Preclinical Evaluation.

Radiotherapy (RT) is the primary standard of care for many locally advanced cancers. Often times, however, the efficacy of RT is limited due to radio-resistance that cancer cells develop. Photodynamic therapy (PDT) has gained importance as an alternative local therapy. Because its mechanism involves minimal acquired resistance, PDT is a useful adjunct to RT. This review discusses recent advances in combining RT with PDT for cancer treatment. In the first part of this review, we will discuss clinical trials on RT + PDT combination therapies. All these approaches suffer from the same inherent limitations as any current PDT methods; (i) visible light has a short penetration depth in human tissue (<∼10 mm), and (ii) it is difficult to illuminate the entire tumor homogeneously by external/interstitial laser irradiation. To address these limitations, scintillating nanoparticle-mediated RT-PDT approaches have been explored in which nanoparticles convert X-rays (RT) into visible light (PDT); high-energy X-rays can reach deep into the body to irradiate cancers uniformly and precisely. The second part of this review will discuss recent efforts in developing and applying nanoparticles for RT-PDT applications.

Efficient plasmon-enhanced perovskite solar cells by molecularly isolated gold nanorods

Perovskite solar cells (PSCs) are becoming a promising candidate for next-generation photovoltaic cells due to their attractive power conversion efficiency (PCE). Plasmonic enhancement is regarded as an optical tuning approach for further improving the PCE of single-junction PSCs toward Shockley-Queisser limit. Herein, we introduce molecularly isolated gold nanorods (Au NRs), bearing relatively stronger scattering ability and localized surface plasmonic resonance (LSPR) effect, in the rear side of perovskites in PSCs, for promoting light harvesting and for electrical enhancement. Owing to the larger refractive index and better matched energy level alignment, the 4-mercaptobenzoic acid molecules coated on Au NRs prove to play important dual roles: isolating the metallic Au NRs from contacting with perovskite, and facilitating more efficient charge separation and transport across the interface under the synergetic LSPR effect of Au NRs. Our work highlights the capability of the plasmonic approach by nanorods and by molecular isolation, extending nanoparticle-based plasmonic approaches, toward highly efficient plasmon-enhanced PSCs.

HER-2-Targeted Nanoparticles for Breast Cancer Diagnosis and Treatment.

Simple SummaryDespite tremendous efforts in finding new therapeutic strategies and promoting screening programs to increase early diagnosis, breast cancer is still a major cause of death in the female worldwide population. Preclinical and clinical evidence have shown that nanotechnologies can significantly contribute to improving both therapeutic and diagnostic aspects. This is particularly true for human epidermal growth factor receptor-2 (HER-2) overexpressing (HER-2+) breast cancer, where recurrence rates and drug resistance still make it one of the most aggressive breast cancer subtypes, despite the development of promising targeted therapies. The aim of this review is to provide an update on the most promising nanoparticle-based approaches developed in the last decade in the context of HER-2-positive breast cancer therapy and diagnosis.Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is a breast cancer subtype characterized by high aggressiveness, high frequency of brain metastases and poor prognosis. HER-2, a glycoprotein belonging to the ErbB receptor family, is overexpressed on the outer membrane of cancer cells and has been an important therapeutic target for the development of targeted drugs, such as the monoclonal antibodies trastuzumab and pertuzumab. These therapies have been available in clinics for more than twenty years. However, despite the initial enthusiasm, a major issue emerged limiting HER-2 targeted therapy efficacy, i.e., the evolution of drug resistance, which could be tackled by nanotechnology. The aim of this review is to provide a first critical update on the different types of HER-2-targeted nanoparticles that have been proposed in the literature in the last decade for therapeutic purposes. We focus on the different targeting strategies that have been explored, their relative outcomes and current limitations that still need to be improved. Then, we review the nanotools developed as diagnostic kits, focusing on the most recent techniques, which allow accurate quantification of HER-2 levels in tissues, with the aim of promoting more personalized medicinal approaches in patients.

Epigallocatechin gallate: Phytochemistry, bioavailability, utilization challenges, and strategies.

Epigallocatechin gallate (EGCG), a green tea catechin, has gained the attention of current study due to its excellent health-promoting effects. It possesses anti-obesity, antimicrobial, anticancer, anti-inflammatory activities, and is under extensive investigation in functional foods for improvement. It is susceptible to lower stability, lesser bioavailability, and lower absorption rate due to various environmental, processing, formulations, and gastrointestinal conditions of the human body. Therefore, it is the foremost concern for the researchers to enhance its bioactivity and make it the most suitable therapeutic compound for its clinical applications. In the current review, factors affecting the bioavailability of EGCG and the possible strategies to overcome these issues are reviewed and discussed. This review summarizes structural modifications and delivery through nanoparticle-based approaches including nano-emulsions, encapsulations, and silica-based nanoparticles for effective use of EGCG in functional foods. Moreover, recent advances to enhance EGCG therapeutic efficacy by specifically targeting its molecules to increase its bioavailability and stability are also described. PRACTICAL APPLICATIONS: The main green tea constituent EGCG possesses several health-promoting effects making EGCG a potential therapeutic compound to cure ailments. However, its low stability and bioavailability render its uses in many disorders. Synthesizing EGCG prodrugs by structural modifications helps against its low bioavailability and stability by overcoming premature degradation and lower absorption rate. This review paper summarizes various strategies that benefit EGCG under different physiological conditions. The esterification, nanoparticle approaches, silica-based EGCG-NPs, and EGCG formulations serve as ideal EGCG modification strategies to deliver superior concentrations with lesser toxicity for its efficient penetration and absorption across cells both in vitro and in vivo. As a result of EGCG modifications, its bioactivities would be highly improved at lower doses. The protected or modified EGCG molecule would have enhanced potential effects and stability that would contribute to the clinical applications and expand its use in various food and cosmetic industries.

Nanotechnology in Immunotherapy for Type 1 Diabetes: Promising Innovations and Future Advances.

Diabetes is a chronic condition which affects the glucose metabolism in the body. In lieu of any clinical “cure,” the condition is managed through the administration of pharmacological aids, insulin supplements, diet restrictions, exercise, and the like. The conventional clinical prescriptions are limited by their life-long dependency and diminished potency, which in turn hinder the patient’s recovery. This necessitated an alteration in approach and has instigated several investigations into other strategies. As Type 1 diabetes (T1D) is known to be an autoimmune disorder, targeting the immune system in activation and/or suppression has shown promise in reducing beta cell loss and improving insulin levels in response to hyperglycemia. Another strategy currently being explored is the use of nanoparticles in the delivery of immunomodulators, insulin, or engineered vaccines to endogenous immune cells. Nanoparticle-assisted targeting of immune cells holds substantial potential for enhanced patient care within T1D clinical settings. Herein, we summarize the knowledge of etiology, clinical scenarios, and the current state of nanoparticle-based immunotherapeutic approaches for Type 1 diabetes. We also discuss the feasibility of translating this approach to clinical practice.

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System.

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.

Adalimumab Decorated Nanoparticles Enhance Antibody Stability and Therapeutic Outcome in Epithelial Colitis Targeting.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with increasing incidence worldwide. Although a deeper understanding of the underlying mechanisms of IBD has led to new therapeutic approaches, treatment options are still limited. Severe adverse events in conventional drug therapy and poor drug targeting are the main cause of early therapy failure. Nanoparticle-based targeting approaches can selectively deliver drugs to the site of inflammation and reduce the risk of side effects by decreasing systemic availability. Here, we developed a nanoparticulate platform for the delivery of the anti-TNF-α antibody adalimumab (ADA) by covalent crosslinking to the particle surface. ADA binding to nanoparticles improved the stability of ADA against proteolytic degradation in vitro and led to a significantly better therapeutic outcome in a murine colitis model. Moreover, immobilization of ADA reduced systemic exposure, which can lead to enhanced therapeutic safety. Thus, nanoparticle protein decoration constitutes a platform through which epithelial delivery of any biological of interest to the inflamed gut and hence a local treatment can be achieved.

Drug Targeting Approaches and Use of Drug Delivery Systems in Management of Cancer.

Mutations and their manifestations in the form of various diseases and disorders result in cancer which is a major cause of human death worldwide. A considerable amount of information is available at the cellular, molecular and genetic levels regarding the occurrence and spread of precarious cancer; yet, there is no cure. The traditional methods of treatment such as chemotherapy, radiotherapy and surgical intervention have shown to be moderately effective and to keep some types of cancer under control, but each modality has its own advantages and disadvantages. In recent years, more advanced methods such as targeted therapies, immunotherapy, and precision medicine are shown to be promising, and these fields continue to expand rapidly along with the conventional methods. This review focuses on the reports of advanced methods of treatment from a scientific standpoint to recognize many new and modern approaches. Selective targeting of the tumour cells by nanoparticle-based novel drug delivery approaches includes the latest innovations in their preparation strategies and applications. The concept of precision medicine and its impact on treatment are highlighted here with the hope of individualised therapy with minimum side effects as a part of ever-expanding treatment strategies. Additional challenges related to cancer treatment like multi-drug resistance and toxicity are also deliberated in brief. Based on the available reports and scientific evidence, better targeted approaches with better quality clinical outcomes and more precise drug delivery to fit individual treatment needs are anticipated in the near future to control this deadly disease.

Nanoparticle-Based Drug Delivery System: The Magic Bullet for the Treatment of Chronic Pulmonary Diseases.

Chronic pulmonary diseases encompass different persistent and lethal diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), asthma, and lung cancers that affect millions of people globally. Traditional pharmacotherapeutic treatment approaches (i.e., bronchodilators, corticosteroids, chemotherapeutics, peptide-based agents, etc.) are not satisfactory to cure or impede diseases. With the advent of nanotechnology, drug delivery to an intended site is still difficult, but the nanoparticle's physicochemical properties can accomplish targeted therapeutic delivery. Based on their surface, size, density, and physical-chemical properties, nanoparticles have demonstrated enhanced pharmacokinetics of actives, achieving the spotlight in the drug delivery research field. In this review, the authors have highlighted different nanoparticle-based therapeutic delivery approaches to treat chronic pulmonary diseases along with the preparation techniques. The authors have remarked the nanosuspension delivery via nebulization and dry powder carrier is further effective in the lung delivery system since the particles released from these systems are innumerable to composite nanoparticles. The authors have also outlined the inhaled particle's toxicity, patented nanoparticle-based pulmonary formulations, and commercial pulmonary drug delivery devices (PDD) in other sections. Recently advanced formulations employing nanoparticles as therapeutic carriers for the efficient treatment of chronic pulmonary diseases are also canvassed.

Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases.

The increasing burden of respiratory diseases caused by microbial infections poses animmense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.

Biosensor Technologies for Early Detection and Quantification of Plant Pathogens.

Plant pathogens are a major reason of reduced crop productivity and may lead to a shortage of food for both human and animal consumption. Although chemical control remains the main method to reduce foliar fungal disease incidence, frequent use can lead to loss of susceptibility in the fungal population. Furthermore, over-spraying can cause environmental contamination and poses a heavy financial burden on growers. To prevent or control disease epidemics, it is important for growers to be able to detect causal pathogen accurately, sensitively, and rapidly, so that the best practice disease management strategies can be chosen and enacted. To reach this goal, many culture-dependent, biochemical, and molecular methods have been developed for plant pathogen detection. However, these methods lack accuracy, specificity, reliability, and rapidity, and they are generally not suitable for in-situ analysis. Accordingly, there is strong interest in developing biosensing systems for early and accurate pathogen detection. There is also great scope to translate innovative nanoparticle-based biosensor approaches developed initially for human disease diagnostics for early detection of plant disease-causing pathogens. In this review, we compare conventional methods used in plant disease diagnostics with new sensing technologies in particular with deeper focus on electrochemical and optical biosensors that may be applied for plant pathogen detection and management. In addition, we discuss challenges facing biosensors and new capability the technology provides to informing disease management strategies.

Tolerogenic Nanoparticles Impacting B and T Lymphocyte Responses Delay Autoimmune Arthritis in K/BxN Mice.

Current treatments for unwanted antibody responses largely rely on immunosuppressive drugs compromising overall immunity. New approaches to achieve antigen-specific tolerance are desirable to avoid unwanted side effects. Several nanoparticle-based approaches that utilize different mechanisms to tolerize the B or T cell arms of the humoral immune response have shown promise for induction of antigen-specific tolerance, raising the possibility that they could work synergistically if combined. Earlier we showed that Siglec-engaging tolerance-inducing antigenic liposomes (STALs) that display both an antigen (Ag) and glycan ligands of the inhibitory co-receptor CD22 (CD22L) lead to robust antigen-specific B cell tolerance to protein antigens in naive mice. In another approach, administration of free Ag with poly(lactic-co-glycolic acid)-rapamycin nanoparticles (PLGA-R) induced robust antigen-specific tolerance through production of regulatory T cells. Here we illustrate that coadministration of STALs together with PLGA-R to naive mice induced more robust tolerance to multiple antigen challenges than either nanoparticle alone. Moreover, in K/BxN mice that develop spontaneous autoimmune arthritis to the self-antigen glucose-6-phosphate-isomerase (GPI), co-delivery of GPI-LP-CD22L and PLGA-R delayed onset of disease and in some mice prevented the disease indefinitely. The results show synergy between B cell-tolerizing STALs and T cell-tolerizing PLGA-R and the potential to induce tolerance in early stage autoimmune disease.