Search Results (79)

Being one of the most aggressive primary brain tumors, glioblastoma multiforme (GBM) is known from the median survivals of just 15 months following diagnosis. Conventional treatments, including surgical resection, radiotherapy, and chemotherapy, have limited efficiency due to the invasive nature of glioma cells and the presence of a blood–brain barrier. Therefore, adjuvant therapy in the form of a localized delivery of chemotherapeutic agents is indispensable to increase the chances of patients. Among a variety of advanced drug carriers, collagen has recently emerged as an excellent choice for regional chemotherapy, mainly due to its biocompatibility, biodegradability, weak antigenicity, biomimetics, and well-known safety profile, as well as its native presence in the extracellular matrix of the central nervous system. The aim of this paper is to highlight the most recent studies describing the application of collagen as a drug carrier able to provide an extended delivery of chemotherapeutic agents directly to the GBM site, and to provide exciting opportunities for its future applications. Full article

Background: Vaccines have revolutionized disease prevention, yet their effectiveness is challenged by variable immunogenicity, individual response differences, and emerging variants. Biomimetic strategies, inspired by natural immune processes, offer new avenues to enhance vaccine performance. Objectives: This narrative review examines how bioinspired approaches—grounded in evolutionary medicine, immunology, and host–microbiota interactions—can improve vaccine immunogenicity and long-term protection. We further examine the evolutionary foundations of immune responses, highlighting how an evolutionary perspective can inform the development of durable, broadly protective, and personalized vaccines. Furthermore, mechanistic insights at the molecular and cellular level are explored, including Toll-like receptor (TLR) engagement, dendritic cell activation pathways, and MHC-I/MHC-II-mediated antigen presentation. These mechanisms are often mimicked in biomimetic systems to enhance uptake, processing, and adaptive immune activation. Results: The review highlights how immunosenescence, maternal immunity, genetic variation, and gut microbiota composition influence vaccine responses. Biomimetic platforms—such as nanoparticle carriers and novel adjuvants—enhance antigen presentation, boost adaptive immunity, and may overcome limitations in traditional vaccine approaches. Additionally, co-administration strategies, delivery systems, and microbiota-derived immunomodulators show promise in improving vaccine responsiveness. Conclusions: Integrating biomimetic and evolutionary principles into vaccine design represents a promising path toward safer, longer-lasting, and more effective immunizations Full article

Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article

The emergence of complex and rapidly evolving pathogens necessitates innovative vaccine platforms that move beyond traditional methods. This review explores the transformative potential of next-generation vaccine technologies, focusing on the combined use of synthetic biology, nanotechnology, and systems immunology. Synthetic biology provides modular tools for designing antigenic components with improved immunogenicity, as seen in mRNA, DNA, and peptide-based platforms featuring codon optimization and self-amplifying constructs. At the same time, nanotechnology enables precise antigen delivery and controlled immune activation through engineered nanoparticles such as lipid-based carriers, virus-like particles, and polymeric systems to improve stability, targeting, and dose efficiency. Systems immunology aids these advancements by analyzing immune responses through multi-omics data and computational modeling, which assists in antigen selection, immune profiling, and adjuvant optimization. This approach enhances both humoral and cellular immunity, solving challenges like antigen presentation, response durability, and vaccine personalization. Case studies on SARS-CoV-2, Epstein–Barr virus, and Mycobacterium tuberculosis highlight the practical application of these platforms. Despite promising progress, challenges include scalability, safety evaluation, and ethical concerns with data-driven vaccine designs. Ongoing interdisciplinary collaboration is crucial to fully develop these technologies for strong, adaptable, globally accessible vaccines. This review emphasizes next-generation vaccines as foundational for future immunoprophylaxis, especially against emerging infectious diseases and cancer immunotherapy. Full article

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8⁺ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8⁺ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article

Background: Diabetic foot osteomyelitis is a complex condition to manage, with substantial risk of treatment failure, which could necessitate major amputations. Surgical debridement and prolonged systemic antibiotic therapy have been the mainstay of treatment, but recurrence rates remain high. The use of adjuvant local antibiotic therapy has been proposed as a potential adjunct to improve outcomes. Methods: This retrospective study involved 113 patients with diabetic foot osteomyelitis, who underwent debridement and application of antibiotic-loaded hydroxyapatite ceramic from the year 2018 to 2023. Clinical outcomes of interest were eradication of infection, ulcer healing, recurrence of infection, prevention of major amputation and mortality rate. Patient-associated factors were identified and analysed. Results: Eradication of infection was achieved in 96%, healing of ulcer in 93% and limb salvage in 95% of patients. The mortality rate at 1 year was 5.4%. Peripheral arterial disease, HbA1c and CRP levels were statistically significant in affecting treatment outcomes. Other factors had no impact on the treatment success. Conclusions: This is the largest single-centre study involving Cerament G and V in the management of diabetic foot osteomyelitis and the first investigating the specific factors associated with outcome goals. The use of these antibiotic-loaded carriers demonstrated excellent eradication of infection, healing of ulcer and limb salvage and prevention of recurrence of infection. Full article

Background: The majority of antigen-based SARS-CoV-2 (SCV2) vaccines utilized in the clinic have had the Spike protein or domains thereof as the immunogen. While the Spike protein is highly immunogenic, it is also subject to genetic drift over time, which has led to a series of variants of concern that continue to evolve, requiring yearly updates to the vaccine formulations. In this study, we investigate the potential of the N-terminal ectodomain of the ORF3a protein encoded by the orf3a gene of SCV2 to be an evolution-resistant vaccine antigen. This domain is highly conserved over time, and, unlike many other SCV2 conserved proteins, it is present on the exterior of the virion, making it accessible to antibodies. ORF3a is also important for eliciting robust anti-SARS-CoV-2 T-cell responses. Methods: We designed a DNA vaccine by fusing the N-terminal ectodomain of orf3a to macrophage-inflammatory protein 3α (MIP3α), which is a chemokine utilized in our laboratory that enhances vaccine immunogenicity by targeting an antigen to its receptor CCR6 present on immature dendritic cells. The DNA vaccine was tested in mouse immunogenicity studies, vaccinating by intramuscular (IM) electroporation and by intranasal (IN) with CpG adjuvant administrations. We also tested a peptide vaccine fusing amino acids 15–28 of the ectodomain to immunogenic carrier protein KLH, adjuvanted with Addavax. Results: The DNA IM route was able to induce 3a-specific splenic T-cell responses, showing proof of principle that the region can be immunogenic. The DNA IN route further showed that we could induce ORF3a-specific T-cell responses in the lung, which are critical for potential disease mitigation. The peptide vaccine elicited a robust anti-ORF3a antibody response systemically, as well as in the mucosa of the lungs and sinus cavity. Conclusions: These studies collectively show that this evolutionarily stable region can be targeted by vaccination strategies, and future work will test if these vaccines, alone or in combination, can result in reduced disease burden in animal challenge models. Full article

Pesticide use in crops is a severe problem in some countries. Each country has its legislation for use, but they differ in the degree of tolerance for these broadly toxic products. Several synthetic pesticides can cause air, soil, and water pollution, contaminating the human food chain and other living beings. In addition, some of them can accumulate in the environment for an indeterminate amount of time. The agriculture sector must guarantee healthy food with sustainable production using environmentally friendly methods. In this context, biological biopesticides from microbes and plants are a growing green solution for this segment. Several pests attack crops worldwide, including weeds, insects, nematodes, and microorganisms such as fungi, bacteria, and viruses, causing diseases and economic losses. The use of bioproducts from microorganisms, such as microbial biopesticides (MBPs) or microorganisms alone, is a practice and is growing due to the intense research in the world. Mainly, bacteria, fungi, and baculoviruses have been used as sources of biomolecules and secondary metabolites for biopesticide use. Different methods, such as direct soil application, spraying techniques with microorganisms, endotherapy, and seed treatment, are used. Adjuvants like surfactants, protective agents, and carriers improve the system in different formulations. In addition, microorganisms are a tool for the bioremediation of pesticides in the environment. This review summarizes these topics, focusing on the biopesticides of microbial origin. Full article

The intersection of immunology and nanotechnology has provided significant advancements in biomedical research and clinical applications over the years. Immunology aims to understand the immune system’s defense mechanisms against pathogens. Nanotechnology has demonstrated its potential to manipulate immune responses, as nanomaterials’ properties can be modified for the desired application. Research has shown that nanomaterials can be applied in diagnostics, therapy, and vaccine development. In diagnostics, nanomaterials can be used for biosensor development, accurately detecting biomarkers even at very low concentrations. Therapeutically, nanomaterials can act as efficient carriers for delivering drugs, antigens, or genetic material directly to targeted cells or tissues. This targeted delivery improves therapeutic efficacy and reduces the adverse effects on healthy cells and tissues. In vaccine development, nanoparticles can improve vaccine durability and extend immune responses by effectively delivering adjuvants and antigens to immune cells. Despite these advancements, challenges regarding the safety, biocompatibility, and scalability of nanomaterials for clinical applications are still present. This review will cover the fundamental interactions between nanomaterials and the immune system, their potential applications in immunology, and their safety and biocompatibility concerns. Full article

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5′cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases. Full article

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. Full article

The opportunistic bacteria growing in biofilms play a decisive role in the pathogenesis of chronic infectious diseases. Biofilm-dwelling bacteria behave differently than planktonic bacteria and are likely to increase resistance and tolerance to antimicrobial therapeutics. Antimicrobial adjuvants have emerged as a promising strategy to combat antimicrobial resistance (AMR) and restore the efficacy of existing antibiotics. A combination of antibiotics and potential antimicrobial adjuvants, (e.g., extracellular polymeric substance (EPS)-degrading enzymes and quorum sensing inhibitors (QSI) can improve the effects of antibiotics and potentially reduce bacterial resistance). In addition, encapsulation of antimicrobials within nanoparticulate systems can improve their stability and their delivery into biofilms. Lipid nanocarriers (LNCs) have been established as having the potential to improve the efficacy of existing antibiotics in combination with antimicrobial adjuvants. Among them, liquid crystal nanoparticles (LCNPs), liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) are promising due to their superior properties compared to traditional formulations, including their greater biocompatibility, higher drug loading capacity, drug protection from chemical or enzymatic degradation, controlled drug release, targeted delivery, ease of preparation, and scale-up feasibility. This article reviews the recent advances in developing various LNCs to co-deliver some well-studied antimicrobial adjuvants combined with antibiotics from different classes. The efficacy of various combination treatments is compared against bacterial biofilms, and synergistic therapeutics that deserve further investigation are also highlighted. This review identifies promising LNCs for the delivery of combination therapies that are in recent development. It discusses how LNC-enabled co-delivery of antibiotics and adjuvants can advance current clinical antimicrobial treatments, leading to innovative products, enabling the reuse of antibiotics, and providing opportunities for saving millions of lives from bacterial infections. Full article

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile’s effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy. Full article

Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines. Full article

Hemlock wooly adelgid (Adelgis tsugae Annand) (HWA) has invaded much of eastern hemlock’s (Tsugae canadensis L. Carrière) native range. Arborists and forest managers have successfully handled this pest using either contact or systemic pesticides. One of these pesticides, imidacloprid, has often been applied using a soil or trunk injection. Although imidacloprid has been labeled as a basal bark spray to control HWA, minimal information regarding its efficacy is available. This study compared bark treatments to soil treatment of imidacloprid at high and low application rates, as well as the use of a bark adjuvant. The results showed that basal bark treatments were as effective as soil treatments. Hence, basal bark treatments of imidacloprid can be an effective method for control of HWAs in eastern hemlock trees. A bark adjuvant may not be necessary, as it was not found to influence the amount of imidacloprid in the tissues. Full article