Nano-vaccines combining customized in situ anti-PD-L1 depot for enhanced tumor immunotherapy.

Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment.

Evaluating the immunogenicity of gold nanoparticles conjugated RBD with Freund's adjuvant as a potential vaccine against SARS-CoV-2.

BACKGROUND: and Introduction: SARS-CoV-2 is currently considered as the most challenging issue in the field of health and medicine by causing a global pandemic. Vaccines are counted as a promising candidate to terminate this deadly pandemic. Various structural proteins in SARS-CoV-2 have recently drawn attention to be utilized as candidate vaccines to stimulate immune responses against COVID-19. MATERIALS AND METHODS: In current study, the RBD protein was cloned and expressed in E. coli host. Then, the expressed RBD protein was purified and its characterizations were evaluated through various methods. Gold nanoparticles, which were utilized as a carrier for candidate Nano-vaccine, were synthesized via oxidation-reduction reaction. While Gold NPs-conjugated RBD was injected into the second treatment group, in the first candidate vaccine, RBD was injected into the first treatment group solely. Complete and Incomplete Freud's Adjuvant were also utilized for both treatment groups to enhance the immune responses against RBD antigen. Immunizations were repeated 2 times in 14-day intervals to boost the immune system of BALB/c mice. The humoral and cell-mediated immune responses were examined through immune and cytokine assays. RESULTS: Our outcomes demonstrate that strong short-term humoral immunity (IgM) was induced in both the first and second treatment group, while long-term humoral responses (IgG) were only observed in the second treatment group. While stronger short- and long-term humoral (IgM and IgG, respectively) were observed in the second treatment group, particular cytokines production (TNF-ɑ and IFN-γ) as a marker of cell-mediated responses were significantly higher in the first treatment group. DISCUSSION AND CONCLUSION: Our study results show the high potentiality of RBD protein as an appropriate stimulating antigen in vaccine synthesis and testifies RBD-based candidate vaccines to control the COVID-19 pandemic. Our outcomes also recommend that Nano-vaccines can be more suitable candidates when stronger long-term immune responses matter.

How can nanotechnology help to combat COVID-19? Opportunities and urgent need.

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.

Hybrid mRNA Nano Vaccine Potentiates Antigenic Peptide Presentation and Dendritic Cell Maturation for Effective Cancer Vaccine Therapy and Enhances Response to Immune Checkpoint Blockade.

Cancer vaccines combined with immune checkpoint blockades (ICB) represent great potential application, yet the insufficient tumor antigen presentation and immature dendritic cells hinder improved efficacy. Here, a hybrid nano vaccine composed by hyper branched poly(beta-amino ester), modified iron oxide nano adjuvant and messenger RNA (mRNA) encoded with model antigen ovalbumin (OVA) is presented. The nano vaccine outperforms three commercialized reagents loaded with the same mRNA, including Lipofectamine MessengerMax, jetPRIME, and in vivo-jetRNA in promoting dendritic cells' transfection, maturation, and peptide presentation. In an OVA-expressing murine model, intratumoral administration of the nano vaccine significantly induced macrophages and dendritic cells' presenting peptides and expressing co-stimulatory CD86. The nano vaccine also elicited strong antigen-specific splenocyte response and promoted CD8+ T cell infiltration. In combination with ICB, the nano vaccine aroused robust tumor suppression in murine models with large tumor burdens (initial volume >300 mm3 ). The hybrid mRNA vaccine represents a versatile and readily transformable platform and augments response to ICB.

Nanoparticulate drugs and vaccines: Breakthroughs and bottlenecks of repurposing in breast cancer.

Breast cancer (BC) is a highly diagnosed and topmost cause of death in females worldwide. Drug repurposing (DR) has shown great potential against BC by overcoming major shortcomings of approved anticancer therapeutics. However, poor physicochemical properties, pharmacokinetic performance, stability, non-selectivity to tumors, and side effects are severe hurdles in repurposed drug delivery against BC. The variety of nanocarriers (NCs) has shown great promise in delivering repurposed therapeutics for effective treatment of BC via improving solubility, stability, tumor selectivity and reducing toxicity. Besides, delivering repurposed cargos via theranostic NCs can be helpful in the quick diagnosis and treatment of BC. Localized delivery of repurposed candidates through apt NCs can diminish the systemic side effects and improve anti-tumor effectiveness. However, breast tumor variability and tumor microenvironment have created several challenges to nanoparticulate delivery of repurposed cargos. This review focuses on DR as an ingenious strategy to treat BC and circumvent the drawbacks of approved anticancer therapeutics. Various nanoparticulate avenues delivering repurposed therapeutics, including non-oncology cargos and vaccines to target BC effectively, are discussed along with case studies. Moreover, clinical trial information on repurposed medications and vaccines for the treatment of BC is covered along with various obstacles in nanoparticulate drug delivery against cancer that have been so far identified. In a nutshell, DR and drug delivery of repurposed drugs via NCs appears to be a propitious approach in devastating BC.

Protein Informatics and Vaccine Development: Cancer Case Study.

Clinical translation is a challenging step in the development of cancer vaccines and is found to be related to the complex nature of cancer immunology. Vaccine-based therapeutic strategies for cancer have gained consideration with the advent of vaccine technology as well as an understanding of cancer immunology. Immunotherapy has been widely used in the treatment of cancer. Some promising candidates have been identified to engineer cancer vaccines like Glycoprotein, Mucin 1, MHC protein, etc. It has benefited from the availability of advanced techniques for rapid identification and selection of proteins for precision engineering. Simultaneously, nanovaccines have been focused on target delivery and artificial intelligence-based approaches for personalized vaccine development. The manuscript summarizes the advances in the development of structurebased cancer vaccines along with the status of clinical studies and applications.

Engineered nanomaterials as fighters against SARS-CoV-2: The way to control and treat pandemics.

In this editorial trend, we aim to collect and present recently available data about the characteristics of SARS-CoV-2 virus, severity, infection, replication, diagnosis, and current medications. In addition, we propose the role of nanomaterials in controlling and treating COVID-19 through their antiviral and antibacterial potential with suggested action mechanisms indicating the capability of interaction between these nanomaterials and SARS-CoV-2. These nanomaterials might be among the possible and most effective cures against coronavirus.

Advances in Engineered Polymer Nanoparticle Tracking Platforms towards Cancer Immunotherapy-Current Status and Future Perspectives.

Engineering polymeric nanoparticles for their shape, size, surface chemistry, and functionalization using various targeting molecules has shown improved biomedical applications for nanoparticles. Polymeric nanoparticles have created tremendous therapeutic platforms, particularly applications related to chemo- and immunotherapies in cancer. Recently advancements in immunotherapies have broadened this field in immunology and biomedical engineering, where "immunoengineering" creates solutions to target translational science. In this regard, the nanoengineering field has offered the various techniques necessary to manufacture and assemble multifunctional polymeric nanomaterial systems. These include nanoparticles functionalized using antibodies, small molecule ligands, targeted peptides, proteins, and other novel agents that trigger and encourage biological systems to accept the engineered materials as immune enhancers or as vaccines to elevate therapeutic functions. Strategies to engineer polymeric nanoparticles with therapeutic and targeting molecules can provide solutions for developing immune vaccines via maintaining the receptor storage in T- and B cells. Furthermore, cancer immunotherapy using polymeric nanomaterials can serve as a gold standard approach for treating primary and metastasized tumors. The current status of the limited availability of immuno-therapeutic drugs highlights the importance of polymeric nanomaterial platforms to improve the outcomes via delivering anticancer agents at localized sites, thereby enhancing the host immune response in cancer therapy. This review mainly focuses on the potential scientific enhancements and recent developments in cancer immunotherapies by explicitly discussing the role of polymeric nanocarriers as nano-vaccines. We also briefly discuss the role of multifunctional nanomaterials for their therapeutic impacts on translational clinical applications.

The Importance of Nanocarrier Design and Composition for an Efficient Nanoparticle-Mediated Transdermal Vaccination.

The World Health Organization estimates that the pandemic caused by the SARS-CoV-2 virus claimed more than 3 million lives in 2020 alone. This situation has highlighted the importance of vaccination programs and the urgency of working on new technologies that allow an efficient, safe, and effective immunization. From this perspective, nanomedicine has provided novel tools for the design of the new generation of vaccines. Among the challenges of the new vaccine generations is the search for alternative routes of antigen delivery due to costs, risks, need for trained personnel, and low acceptance in the population associated with the parenteral route. Along these lines, transdermal immunization has been raised as a promising alternative for antigen delivery and vaccination based on a large absorption surface and an abundance of immune system cells. These features contribute to a high barrier capacity and high immunological efficiency for transdermal immunization. However, the stratum corneum barrier constitutes a significant challenge for generating new pharmaceutical forms for transdermal antigen delivery. This review addresses the biological bases for transdermal immunomodulation and the technological advances in the field of nanomedicine, from the passage of antigens facilitated by devices to cross the stratum corneum, to the design of nanosystems, with an emphasis on the importance of design and composition towards the new generation of needle-free nanometric transdermal systems.

Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers.

The broad relationship between the immune system and cancer is opening a new hallmark to explore for nanomedicine. Here, all the common and synergy points between both areas are reviewed and described, and the recent approaches which show the progress from the bench to the beside to biomarkers developed in nanomedicine and onco-immunotherapy.

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines.

The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. "Wild-type" viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity.

Calcium Phosphate Nanoparticle-Based Vaccines as a Platform for Improvement of HIV-1 Env Antibody Responses by Intrastructural Help.

Incorporation of immunodominant T-helper epitopes of licensed vaccines into virus-like particles (VLP) allows to harness T-helper cells induced by the licensed vaccines to provide intrastructural help (ISH) for B-cell responses against the surface proteins of the VLPs. To explore whether ISH could also improve antibody responses to calcium phosphate (CaP) nanoparticle vaccines we loaded the nanoparticle core with a universal T-helper epitope of Tetanus toxoid (p30) and functionalized the surface of CaP nanoparticles with stabilized trimers of the HIV-1 envelope (Env) resulting in Env-CaP-p30 nanoparticles. In contrast to soluble Env trimers, Env containing CaP nanoparticles induced activation of naïve Env-specific B-cells in vitro. Mice previously vaccinated against Tetanus raised stronger humoral immune responses against Env after immunization with Env-CaP-p30 than mice not vaccinated against Tetanus. The enhancing effect of ISH on anti-Env antibody levels was not attended with increased Env-specific IFN-γ CD4 T-cell responses that otherwise may potentially influence the susceptibility to HIV-1 infection. Thus, CaP nanoparticles functionalized with stabilized HIV-1 Env trimers and heterologous T-helper epitopes are able to recruit heterologous T-helper cells induced by a licensed vaccine and improve anti-Env antibody responses by intrastructural help.

Polysaccharides as vaccine adjuvants.

Adjuvant is a substance added to vaccine to improve the immunogenicity of antigens, and it can induce stronger immune responses and reduce the dosage and production cost of vaccine in populations responding poorly to vaccination. Adjuvants in development or in use mainly include aluminum salts, oil emulsions, saponins, immune-stimulating complexes, liposomes, microparticles, nonionic block copolymers, polysaccharides, cytokines and bacterial derivatives. Polysaccharide adjuvants have attracted much attention in the preparation of nano vaccines and nano drugs because natural polysaccharides have the characteristics of intrinsic immunomodulating, biocompatibility, biodegradability, low toxicity and safety. Moreover, it has been proved that a variety of natural polysaccharides possess better immune promoting effects, and they can enhance the effects of humoral, cellular and mucosal immunities. In the present study, we systematically reviewed the recent studies on polysaccharides with vaccine adjuvant activities, including chitosan-based nanoparticles (NPs), glucan, mannose, inulin polysaccharide and Chinese medicinal herb polysaccharide. The application and future perspectives of polysaccharides as adjuvants were also discussed. These findings lay a foundation for the further development of polysaccharide adjuvants. Collectively, more and more polysaccharide adjuvants will be developed and widely used in clinical practice with more in-depth investigations of polysaccharide adjuvants.