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Chiral materials with the same atomic compositions exhibit different chemical, physical, and biological properties because of their distinct spatial structures. Herein, a chiral strategy was proposed to develop poly(lactic acid) (PLA) nanoparticle as an efficient nanoadjuvant to activate adaptive anticancer immunity. Two chiral nanovaccines were prepared by directly mixing amino-terminated PLA (PLLA-NH 2 or PDLA-NH 2 ) with the model protein antigen ovalbumin (OVA). After being injected into mice subcutaneously, both nanovaccines efficiently migrated to the lymph nodes to initiate the sequential anticancer immune responses. Compared with the PLLA nanovaccine (PLLA-OVA), the PDLA one (PDLA-OVA) contributed to more robust dendritic cell (DC) maturation, antigen presentation, and T lymphocyte activation. In addition to the activation of cellular immunity, PDLA-OVA also triggered a more vigorous activation of humoral immunity, which induced the production of more anti-OVA immunoglobulin G (IgG) than PLLA-OVA. When used as prophylactic or therapeutic nanovaccine toward murine melanoma models, PDLA-OVA triggered more potent adaptive anticancer immune responses that more effectively inhibited the cancer genesis and progression, indicating the significant potential of immunologically effective PDLA nanoadjuvant in cancer immunotherapy.

[Display omitted] •Q. brasiliensis QB-80 saponins revealed chemical similarities to the commercial Q. saponaria barks-extracted saponin.•The QB-80 saponins were able to self-assembly with lipids in ISCOM-like nanoparticle named IMXQB-80.•Subcutaneous administration of QB-80 and IMXQB-80 induced high titres of anti-Zika virus with neutralizing antibodies. Vaccine adjuvants are compounds that enhance/prolong the immune response to a co-administered antigen. Saponins have been widely used as adjuvants for many years in several vaccines – especially for intracellular pathogens – including the recent and somewhat revolutionary malaria and shingles vaccines. In view of the immunoadjuvant potential of Q. brasiliensis saponins, the present study aimed to characterize the QB-80 saponin-rich fraction and a nanoadjuvant prepared with QB-80 and lipids (IMXQB-80). In addition, the performance of such adjuvants was examined in experimental inactivated vaccines against Zika virus (ZIKV). Analysis of QB-80 by DI-ESI-ToF by negative ion electrospray revealed over 29 saponins that could be assigned to known structures existing in their congener Q. saponaria, including the well-studied QS-21 and QS-7. The QB-80 saponins were a micrOTOF able to self-assembly with lipids in ISCOM-like nanoparticles with diameters of approximately 43 nm, here named IMXQB-80. Toxicity assays revealed that QB-80 saponins did present some haemolytical and cytotoxic potentials; however, these were abrogated in IMXQB-80 nanoparticles. Regarding the adjuvant activity, QB-80 and IMXQB-80 significantly enhanced serum levels of anti-Zika virus IgG and subtypes (IgG1, IgG2b, IgG2c) as well as neutralized antibodies when compared to an unadjuvanted vaccine. Furthermore, the nanoadjuvant IMXQB-80 was as effective as QB-80 in stimulating immune responses, yet requiring fourfold less saponins to induce the equivalent stimuli, and with less toxicity. These findings reveal that the saponin fraction QB-80, and particularly the IMXQB-80 nanoadjuvant, are safe and capable of potentializing immune responses when used as adjuvants in experimental ZIKV vaccines.

The invention of new techniques to manipulate materials at their nanoscale had an evolutionary effect on various medical sciences. At the time, there are thousands of nanomaterials which can be divided according to their shape, origin, or their application. The nanotechnology provided new solutions for old problems. In medical sciences, they are used for diagnostic or therapeutic purposes. They can also be applied in the preparation of nanovaccines and nanoadjuvants. Their use in the treatment of cancer and in gene therapy opened the door for a new era in medicine. Recently, various applications of nanotechnology started to find their way in the veterinary sector. They increasingly invade animal therapeutics, diagnostics, production of veterinary vaccines, farm disinfectants, for animal breeding and reproduction, and even the field of animal nutrition. Their replacement of commonly used antibiotics directly reflects on the public health. By so doing, they minimize the problem of drug resistance in both human and veterinary medicine, and the problem of drug residues in milk and meat. In addition, they have a great economic impact, by minimizing the amounts of discarded milk and the number of culled calves in dairy herds. Nanotechnology was also applied to develop pet care products and hygienic articles. The present review discusses the advantage of using nanomaterials compared to their counterparts, the various classes of nanoparticles, and illustrates the applications and the role of nanotechnology in the field of veterinary medicine.

Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood–brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype. However, systemic administration of IL-12 toxicity in clinical trials often leads to significant toxicity, posing a critical hurdle. To overcome this major drawback, we have formulated a novel nanoadjuvant composed of immunostimulatory nanoparticles (ISN) loaded with IL-12 to decrease IL-12 toxicity and enhance the immune response by macrophages and GBM cancer cells. Our in vitro results reveal that ISN substantially increase the production of pro-inflammatory cytokines in GBM cancer cells (e.g. 2.6 × increase in IL-8 expression compared to free IL-12) and macrophages (e.g. 2 × increase in TNF-α expression and 6 × increase in IL-6 expression compared to the free IL-12). These findings suggest a potential modulation of the tumor microenvironment. Additionally, our study demonstrates the effective intracellular delivery of IL-12 by ISN, triggering alterations in the levels of pro-inflammatory cytokines at both transcriptional and protein expression levels. These results highlight the promise of the nanoadjuvant as a prospective platform for resharing the GBM microenvironment and empowering immunotherapy. Graphical Abstract

The effectiveness of Toll‐like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti‐tumor immunity. To address that, the common nutrient metal ions are explored (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING‐NF‐κB pathway. Mn2+ and CpG are then self‐assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma‐bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2‐type tumor‐associated macrophages (TAMs) to an M1‐type and boosting intra‐tumoral infiltration of CD8+/CD4+ T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen‐specific cytotoxic CD8+ T cell immune response and humoral immunity. In a prophylactic tumor‐bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16‐OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors. The effectiveness of CpG as an immune adjuvant for tumor immunotherapy is enhanced by the addition of Mn2+ through the activation of the STING‐NF‐κB pathway. Then, the nanoadjuvant MPN/CpG is formed by the self‐assembly of Mn2+ and CpG with the coordination of epigallocatechin gallate (EGCG)and significantly inhibits tumor growth and prolongs the animal survival in a B16 melanoma model. The tumor microenvironment is reshaped by MPN/CpG with increased T cell and dendritic cell (DC) infiltration, enhanced antigen‐specific adaptive immune responses.

Ever since the development of the first vaccine, vaccination has had the great impact on global health, leading to the decrease in the burden of numerous infectious diseases. However, there is a constant need to improve existing vaccines and develop new vaccination strategies and vaccine platforms that induce a broader immune response compared to traditional vaccines. Modern vaccines tend to rely on certain nanotechnology platforms but are still expected to be readily available and easy for large-scale manufacturing and to induce a durable immune response. In this review, we present an overview of the most promising nanoadjuvants and nanoparticulate delivery systems and discuss their benefits from tehchnological and immunological standpoints as well as their objective drawbacks and possible side effects. The presented nano alums, silica and clay nanoparticles, nanoemulsions, adenoviral-vectored systems, adeno-associated viral vectors, vesicular stomatitis viral vectors, lentiviral vectors, virus-like particles (including bacteriophage-based ones) and virosomes indicate that vaccine developers can now choose different adjuvants and/or delivery systems as per the requirement, specific to combatting different infectious diseases.

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression and transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi‐immune pathway regulation strategy through PD‐L1, collagen, and TGF‐β co‐depression. Then, IR‐LND is prepared by combining the mitochondria‐targeted molecule IR‐68 with LND, which then is loaded with liposomes (Lip) to create IR‐LND@Lip nanoadjuvants. By doing this, IR‐LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition. In conclusion, the combined treatment of RT and IR‐LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors. In this research, IR‐LND@Lip is prepared by conjugating heptamethylene cyanine with Lonidamine to lower the dosage of Lonidamine needed in disrupting mitochondrial oxidative phosphorylation. By doing this, IR‐LND@Lip more effectively sensitizes radiotherapy by generating more DNA damage and transforming cold tumors into hot ones through hypoxia reversion and immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition.

Nucleic acid-based adjuvants have recently emerged as promising candidates for use in cancer vaccines to induce tumor-suppressing immune cells. In this study, we tested whether complexation of a nucleic acid-based adjuvant with chitosan (CTS) modulates immune adjuvant functions. As a nucleic acid-based adjuvant, we used toll-like receptor 3-recognizing RNA adjuvant (RA). Negatively charged RA formed nanoscale polyplexes with cationic CTS that possessed positive zeta potentials. RA/CTS polyplexes exerted dendritic cell (DC)-maturation effects without causing significant DC toxicity. This DC-maturation effect was CTS molecular weight dependent, with RA/CTS polyplexes with a CTS molecular weight of 340 kDa (RA/CTS 340K) producing the greatest effect. Subcutaneous injection of RA/CTS 340K polyplexes with the model tumor antigen ovalbumin exerted a preventive effect against challenge by ovalbumin-expressing tumor cells. It also provided greater inhibitory effects against a second challenge with the same tumor cells compared with other treatments. These protective effects of subcutaneous RA/CTS polyplex treatment were associated with the highest tumor antigen-specific humoral and cellular immune responses after tumor challenge, and with the greatest infiltration of CD4 helper T cell and CD8 T cell into the tumor tissues. Mice vaccinated with ovalbumin and RA/CTS polyplexes showed complete survival, even after repeated challenge with tumor cells. Our results suggest the potential of RA/CTS polyplexes as effective nanoadjuvants in the design of tumor vaccines and cancer immunotherapy.

Background Tuberculosis (TB) is a contagious disease and the second leading cause of death worldwide. The Bacille Calmette–Guérin (BCG) vaccine, the only licensed TB vaccine, has insufficient protective efficacy in adults, necessitating the development of new TB vaccines. Ag85B, a protein-subunit TB vaccine, is a promising candidate due to its high immunogenicity. However, its hydrophobicity presents challenges in manufacturing, expression, and purification, and Ag85B alone does not elicit sufficient immune stimulation. To overcome these limitations, this study aimed to design a temperature-responsive amine-terminated polylactic acid (PLA)-based nanosponge (aPNS) as both a nanoadjuvant and an efficient delivery carrier for Ag85B. Methods Ag85B was produced using an EZtag fusion tag vector, achieving high product yield and purity. It was then loaded into aPNS, a nanoparticle system with a PLA core and Pluronic shell, through a temperature-responsive process at 4 °C that preserved protein bioactivity. The stability and sustained-release profile of Ag85B@aPNS were evaluated. In vitro cytotoxicity and cellular uptake studies were conducted using macrophages. Protective efficacy and immunogenicity were assessed in M. tuberculosis -challenged mice and BCG-primed mice. Results The Ag85B protein was successfully produced and loaded into aPNS, which exhibited good colloidal stability and a sustained-release profile. Neither the synthesized Ag85B nor the aPNS showed significant cytotoxicity. aPNS enhanced the cellular uptake of antigens by macrophages. Compared to BCG, Ag85B@aPNS demonstrated superior protective efficacy against M. tuberculosis in mice and improved immunogenicity in BCG-primed mice. Conclusion Ag85B@aPNS is a viable candidate for TB vaccination, showing potential as both a standalone vaccine and a BCG-booster. Its ability to enhance immunogenicity and provide protection highlights its promise in addressing the limitations of current TB vaccines. Plain language summary Tuberculosis (TB) remains a major global health challenge, and while the current BCG vaccine provides some protection, its effectiveness varies and it does not fully prevent the disease in adults. To address this, researchers are developing new vaccines and boosters that enhance the immune system’s ability to fight TB. This study introduces a novel vaccine candidate called Ag85B@aPNS, which combines a TB-specific protein (Ag85B) with a specialized nanoparticle delivery system (aPNS). The researchers designed the aPNS to carry and protect the Ag85B protein, ensuring it remains stable and active for a longer time. These nanoparticles also respond to temperature changes, making them more effective in releasing the protein under human body conditions. Experiments showed that Ag85B@aPNS was safe for cells and enhanced the ability of immune cells to recognize and process the protein. This means the vaccine can better stimulate the immune system without causing harm. In animal studies, the vaccine was tested in mice infected with TB bacteria. Mice that received Ag85B@aPNS had fewer bacteria in their lungs and less lung damage compared to those given the standard BCG vaccine. Furthermore, when used as a booster in BCG-primed mice, the vaccine strengthened the immune response significantly. These findings suggest that Ag85B@aPNS is a promising candidate for improving TB vaccination strategies, either as a replacement for BCG or as a booster to enhance its effects. This could lead to better protection against TB in the future.

Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high‐lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody‐engineered NIR‐II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR‐II photothermal‐ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS‐Nb) is prepared by metallic iron ion‐mediated coordination self‐assembly of D‐A‐D type NIR‐II molecules and loading of glycolysis inhibitor, 2‐deoxy‐D‐glucose (2DG), followed by modification with aPD‐L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR‐II fluorescence/photoacoustic imaging while initiating NIR‐II photothermal‐ferroptosis therapy. The remarkable NIR‐II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti‐tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR‐II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti‐tumor immunotherapy combined with ICB therapy. NIR‐II nanoadjuvants with metabolic reprogramming capability is constructed by metallic iron ion‐mediated coordination self‐assembly. After nanobody‐mediated active targeting and evoking immune checkpoint blockade, nanoadjuvants responsively decompose triggered by acidic tumor microenvironment (TME) and enable synergistic NIR‐II phototheranostics and ferroptosis, provoking anti‐tumor immune responses. The remodeling of the immunosuppressive TME through lactate metabolism regulation further potentiates the efficiency of immunotherapy.