The urgent need for single-dose vaccines to combat infectious diseases in resource-limited regions has driven the development of a novel polysaccharide-enhanced delivery platform. In this study, a single-dose vaccine platform has been successfully built, which employed the Hepatitis B surface antigen as the model antigen, and the dimethyl-dioctadecyl-ammonium bromide/poly (lactic acid) (DDAB/PLA) nanoparticles (NPs) as delivery and adjuvant systems. Subsequently, alginate, a biocompatible polysaccharide, was utilized to fabricate composite microcapsules (MCs) via spray-drying, named Ag@NPs + Ag@NPs-MCs, enabling dual antigen delivery: sustained release from alginate-encapsulated Ag@NPs and immediate release of free HBsAg. The mice immunized with the single-dose vaccine induced a sustained increase in antibody levels, promoted cytokines secretion, and greatly improved immune memory T/B cells during the six-month evaluation of sustained immunity. The single-dose vaccine also induced effective short-term immune protection. These immune-boosting effects could be attributed to the vaccine formulations regulating antigen release behavior and the antigen-depot effect at the injection. Therefore, Ag@NPs + Ag@NPs-MCs is a promising platform for a single-dose vaccine against infection.

Skin aging could lead to dermal collagen loss and elastic fiber degradation, ultimately manifesting as skin laxity. We aimed to counteract this by using poly-L-lactic acid (PLLA) microsphere (MS)-based fillers to facilitate long-term volume restoration through collagen regeneration. However, conventional MSs exhibit limitations such as broad size distribution and surface irregularities, which are frequently associated with significant adverse reactions. This study employed shirasu porous glass (SPG) membrane emulsification to fabricate uniform and well-shaped polyethylene glycol-block-poly (L-lactic acid) (PEG-PLLA) MSs. A single-factor experiment was employed to optimize the parameters. The optimal preparation conditions for PEG-PLLA MSs were as follows: PEG-PLLA concentration of 40 mg/mL, polyvinyl alcohol (PVA) concentration of 0.5%, and magnetic stirring speed of 200 rpm. Under the optimal conditions, the average particle size of PEG-PLLA MSs was 58.982 μm, and the span value (SPAN) was 1.367. In addition, a cytotoxicity assay was performed, and the results revealed no significant toxicity of the MSs toward L929 mouse fibroblasts at concentrations below 500 μg/mL. Furthermore, PEG-PLLA MSs significantly enhanced the production of key extracellular matrix (ECM) components—type I collagen (Col-I), type III collagen (Col-III), and hyaluronic acid (HA)—while simultaneously alleviating cellular oxidative stress responses. This work offers a reliable and reproducible fabrication strategy for developing biocompatible MS fillers with controllable particle sizes.

Although HPV vaccines currently in use with aluminum adjuvants demonstrate significant stimulation of humoral immunity, the weak cellular immune response that they elicit indicates a need for further improvement. On the other hand, not only the poor immune promotion effect inducted by a single adjuvant but also finding an efficient antigen and adjuvant codelivery carriers need to be addressed. Here, a double Toll like receptor agonist (R848, Poly(I:C)) and antigen of HPV16 L1 pentamer were codelivered by using calcium phosphate (CaP) mineralized PLGA microparticles. The results of in vivo experiments indicate that the secretion of specific antibodies and neutralizing antibodies was significantly increased, and T/B cells in lymph nodes were effectively activated. Of particular note is the formation of more germinal centers in vivo stimulated by the formulation. In addition, the cellar immunity is also promoted with a higher level of cytokines secretion as IFN-γ, TNF-α, and IL-12p70. Therefore, the as-prepared formulations are a potential platform for preventing the HPV virus infection.

Poly(lactic acid-lactic acid) (PLGA) has demonstrated significant application potential in tumor-targeted drug delivery systems due to its excellent biocompatibility, degradability, and multifunctionality for loading various therapeutic agents. PLGA nanoparticles (NPs) can achieve targeted delivery to tumor cells through specific surface modifications and stimulus-responsive release mechanisms, significantly enhancing drug accumulation efficiency at tumor sites while reducing toxic side effects on normal tissues. This review systematically summarizes the fundamental physicochemical properties of PLGA materials and recent advances in tumor-targeting strategies for PLGA NPs. It comprehensively elucidates research breakthroughs in PLGA-based delivery systems regarding stimulus-response mechanisms, passive targeting, active targeting, and tumor combination immunotherapy, while revealing the intrinsic logic of synergistic strategies for enhancing targeting efficiency. Finally, from the perspective of clinical translation and individualized oncology, this review conducts an in-depth assessment of the current challenges and looks forward to future research directions, aiming to provide forward-looking guidance for the development of precision nanomedicine.

The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, and there is no definitive treatment for this condition. Studies have shown that antisense oligonucleotide (asODN) targeting nerve growth factor (NGF) can downregulate the level of NGF in the bladder, however, the uptake of NGF asODN by the body is limited. Therefore, this study constructed cationic liposomes (CLs) as a delivery system to carry NGF asODN and evaluated its functional efficacy on the bladder. The results indicated that the optimized CLs/asODN delivery system had an average particle size of approximately 200 nm, an average zeta potential of around +53 mV, and an encapsulation efficiency of over 90% with good stability. Additionally, CLs/asODN significantly facilitated the uptake of asODN fluorescence by the urothelium, with an uptake rate of 14.6%, which was 40.2 times free asODN. In a rat model of IC/BPS, treatment with CLs/asODN reduced voiding frequency, significantly increased maximum cystometric capacity, prolonged inter-contraction interval of the bladder, and improved bladder compliance. Furthermore, hematoxylin-eosin staining and immunohistochemical analysis revealed significantly reduced expression levels of NGF, PACAP, Piezo2, CCL2, IL-6, and TGF-β factors after treatment, indicating that the overexpression of NGF in the bladder could be indirectly blocked by complexing NGF asODN with cationic liposomes. The CLs/asODN prepared in this study improved the adhesion and penetration of the drug at the bladder mucosa site, effectively alleviated bladder dysfunction in rats, and further enhanced the inhibitory effect of asODN on NGF, which may provide a new strategy for the treatment of IC/BPS.

Introduction:Tumor-associated macrophages (TAMs) promote immunosuppression, hindering immune checkpoint blockade and immunotherapy efficacy. To overcome this, we developed a novel multifunctional nanovaccine based on hepatitis B core virus-like particles (HBc VLP) to synergistically remodel the immunosuppressive tumor microenvironment through integrated TAM reprogramming and B7-H3 checkpoint blockade. Methods:The core VLP co-displayed tumor antigen peptide MAGE-A10 and TAM-targeting peptide M2pep via fusion expression. Immunostimulatory CpG oligodeoxynucleotide 1826 (CpG) was encapsulated within VLP. Anti-B7-H3 antibody (αB7-H3) and polyethylene glycol (PEG) were chemically conjugated to the surface for checkpoint blockade and prolonged circulation, forming CpG@VLP-αB7-H3-PEG. Results:Structural characterization using transmission electron microscopy and dynamic light scattering confirmed the hollow spherical self-assembly of VLP. Nanovaccines efficiently targeted TAMs in vitro and in vivo. Following CpG encapsulation (5.60 µg/mg), the nanovaccine reprogrammed M2-like TAMs into an M1-like phenotype. This was achieved by elevating the M1/M2 ratios of CD86/CD206 and MHC II/CD206 to 15.50-fold and 3.11-fold, respectively, as determined by flow cytometry. Further conjugation of αB7-H3 (250 µg/mg) significantly enhanced T-cell activation in TAM-T cell co-culture assays. In B16-F10 melanoma-bearing mice, reprogrammed iNOS+ M1-like macrophages triggered robust antitumor immunity, achieving a tumor inhibition rate of 63.47%. These macrophages also function as antigen-presenting cells and increase the proportion of tumor-infiltrating Granzyme B+CD8+ T cells. αB7-H3 conjugation further boosted infiltrating immune cells, M1-like macrophages, activated CD69+CD4+/CD8+ T cells, and cytotoxic T lymphocytes. PEGylation amplified systemic tumor-specific immunity and increased tumor inhibition by 80.12%. Conclusion:This HBc VLP-based nanovaccine constitutes a pioneering multifunctional platform designed to overcome TAM-mediated immunosuppression through synergistic integration of three modalities: antigen presentation, TAM phenotype reprogramming, and B7-H3 checkpoint blockade. To the best of our knowledge, this is the first nanovaccine architecture to enable coordinated immunomodulation. Its modular design supports the clinical translation of solid tumors and personalized immunotherapy.

Ozonized sunflower oil has been found to have a valuable antimicrobial activity against bacteria, viruses, and fungi. However, delayed cutaneous wound healing, severe adverse skin reactions such as pain, burns, irritation, and unsatisfactory storage stability have limited its clinical use as it is known that the performance of ozonized sunflower oil is reflected by core indicators such as iodine value (IV), peroxide value (PV), and acid value (AV). Aiming to improve the above characteristics, ozone oxidation conditions such as the oil water content of raw materials, stirring speed, and ozonized time were successfully optimized, and the optimized conditions were 5%, 300 rpm, and 6 h, respectively. Additionally, the UHPLC-Q-Exactive Orbitrap MS was used to identify the compounds of sunflower oil and ozonation sunflower oil, and 10 fatty acids were successfully identified. The results clearly indicated that the ozonized sunflower oil prepared under optimized ozonation conditions achieved a high degree of ozonation (II) and a satisfactory PV/AV ratio. These optimized conditions further proved to be valuable in improving not only the storage stability of ozonized sunflower oil for up to six months but also in ensuring its remarkable antimicrobial effects on Staphylococcus aureus and Candida albicans, with a PV of 165.75 mmol/kg achieving a 100% antibacterial efficacy.

Background: Rutin (R) is a bioactive compound with antioxidant and anti-inflammatory properties, but its low bioavailability limits its application. To address this problem, R was encapsulated with whey protein (W) as nanoparticles, and the potential effect and mechanism of rutin–whey protein nanoparticles (RW) on skeletal muscle dysfunction was investigated in D-galactose induced mice. Methods: R was encapsulated with W to form RW, and its characteristics like particle size, encapsulation efficiency, and bioaccessibility were evaluated. In the in vivo study, male C57BL/6J mice were treated with R, W or RW, respectively. The muscle function, hepatic antioxidant capacity, serum inflammatory levels, gut microbiota, and metabolomic profiles of mice were evaluated. Results: RW showed a uniform particle size, with an encapsulation efficiency of 68.7%. In the RW, the bioaccessibility of rutin was approximately 3.3 times that of free rutin. This in vivo study indicated that in comparison with D-galactose induced mice (model group), R, W and RW treatments could enhance hepatic antioxidative capacity and regulate inflammation levels, while W and RW could also increase muscle strength. Among these, RW treatment significantly elevated the hepatic GSH-PX activity and decreased the serum MSTN, TNF-α, and IL-6 levels, which were all markedly better than those of the individual effect of R or W. Such effects of R, W, and RW may be achieved through the modulation of gut microbiota that produced short-chain fatty acids or involved in anti-inflammatory function and the regulation of metabolic profiles associated with amino acid metabolism, aminoacyl-tRNA biosynthesis, etc. Conclusions: RW was found to enhance the bioaccessibility of rutin, and exhibited positive effects on skeletal muscle dysfunction via the modulation of gut microbiota and metabolic pathways. The results of this study may provide new scientific strategy for the utilization of rutin to achieve its health benefits.

For most frequent respiratory viruses, there is an urgent need for a universal influenza vaccine to provide cross-protection against intra- and heterosubtypes. We previously developed an Escherichia coli fusion protein expressed extracellular domain of matrix 2 (M2e) and nucleoprotein, named NM2e, and then combined it with an aluminum adjuvant, forming a universal vaccine. Although NM2e has demonstrated a protective effect against the influenza virus in mice to some extent, further improvement is still needed for the induction of immune responses ensuring adequate cross-protection against influenza. Herein, we fabricated a cationic solid lipid nanoadjuvant using poly(lactic acid) (PLA) and dimethyl-dioctadecyl-ammonium bromide (DDAB) and loaded NM2e to generate an NM2e@DDAB/PLA nanovaccine (Nv). In vitro experiments suggested that bone marrow-derived dendritic cells incubated with Nv exhibited ∼4-fold higher antigen (Ag) uptake than NM2e at 16 h along with efficient activation by NM2e@DDAB/PLA Nv. In vivo experiments revealed that Ag of the Nv group stayed in lymph nodes (LNs) for more than 14 days after initial immunization and DCs in LNs were evidently activated and matured. Furthermore, the Nv primed T and B cells for robust humoral and cellular immune responses after immunization. It also induced a ratio of IgG2a/IgG1 higher than that of NM2e to a considerable extent. Moreover, NM2e@DDAB/PLA Nv quickly restored body weight and improved survival of homo- and heterosubtype influenza challenged mice, and the cross-protection efficiency was over 90%. Collectively, our study demonstrated that NM2e@DDAB/PLA Nv could offer notable protection against homo- and heterosubtype influenza virus challenges, offering the potential for the development of a universal influenza vaccine.

Hypoxia represents a crucial characteristic of the tumor microenvironment, which is closely related to cell proliferation, angiogenesis, and metabolic responses. These factors will further promote tumor progression, increase tumor invasion, and enhance tumor metastasis potential. A hypoxic microenvironment will also inhibit the activity of infiltrated immune cells in the tumor microenvironment, leading to the failure of cancer immunotherapy. Additionally, the hypoxic tumor microenvironment contributes to resistance to conventional therapies and leads to unfavorable prognoses. This review discusses advancements in strategies aimed at ameliorating tumor hypoxia within the microenvironment and modulating immune cell responses against tumors.

Although we have made remarkable achievements in cancer awareness and medical technology, there are still tremendous increases in cancer incidence and mortality. However, most anti-tumor strategies, including immunotherapy, show low efficiency in clinical application. More and more evidence suggest that this low efficacy may be closely related to the immunosuppression of the tumor microenvironment (TME). The TME plays a significant role in tumorigenesis, development, and metastasis. Therefore, it is necessary to regulate the TME during antitumor therapy. Several strategies are developing to regulate the TME as inhibiting tumor angiogenesis, reversing tumor associated macrophage (TAM) phenotype, removing T cell immunosuppression, and so on. Among them, nanotechnology shows great potential for delivering regulators into TME, which further enhance the antitumor therapy efficacy. Properly designed nanomaterials can carry regulators and/or therapeutic agents to eligible locations or cells to trigger specific immune response and further kill tumor cells. Specifically, the designed nanoparticles could not only directly reverse the primary TME immunosuppression, but also induce effective systemic immune response, which would prevent niche formation before metastasis and inhibit tumor recurrence. In this review, we summarized the development of nanoparticles (NPs) for anti-cancer therapy, TME regulation, and tumor metastasis inhibition. We also discussed the prospect and potential of nanocarriers for cancer therapy.

Poly(lactic acid) (PLA) has excellent properties of biodegradability and biocompatibility, which is a US Food and Drug Administration (FDA) approved biopolymer for the preparation of safe and effective vaccines, drugs, and gene delivery systems. However, there still exists a great problem whether and how the end group affects the immune response of PLA vaccines. Therefore, the aim of this study was to evaluate the in vitro and in vivo of immune response of PLA nanoparticles (NPs) with carboxyl (COOH) and ester (COOR) end groups. In vitro experiments suggested COOH NPs could promote the higher phagocytosis and activation of bone marrow dendritic cells (BMDCs) with a lower cytotoxicity. In vivo experiments showed that COOR NPs and COOH NPs could strongly elicit IgG, IgG1, and IgG2a responses both in the short and long-terms. However, the highest T cell and B cell activation, and central memory T cells response was induced by COOH NPs. In addition, the COOH NPs could significantly enhance splenocytes proliferation and cytokines secretion. Thus, the PLA with the COOH end group shows greater potential as efficient carrier materials of NPs for enhancing cellular and humoral immune responses.

2019年,全球暴发了严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)疫情.由 SARS-CoV-2 引起的传染病(Corona Virus Disease 2019,COVID-19)具有极强的传染性及较高的病死率,对人类健康及经济发展造成了极大伤害.疫苗接种是预防和控制SARS-CoV-2传播的主要途径.信使RNA(mRNA)疫苗因具有制备简单、生产周期短、细胞毒性较小等优点而备受关注;最重要的是,mRNA容易实现量产,是应对突发疫情的重要手段之一.在此将对mRNA疫苗及其作用机制、递送载体以及给药方式等进行综述,旨在为mRNA疫苗研发工作提供参考.

Abstract In developing countries where females are threatened by HPV, reducing the costs of production and transport of HPV vaccine is still one of pressing issues that needs a sustainable solution. Although HPV vaccines currently in use with aluminum adjuvants demonstrate significant stimulation of humoral immunity, the weak cellular immune response they elicit indicates a need for further improvement. On the other hand, the issue of poor immune promotion effect of single use of toll-like receptor agonists also needs to be addressed. Here, a double Toll like receptor agonist (R848, Poly (I:C)) HPV vaccine, with HPV16 L1 pentamer as antigen, was fabricated by using calcium phosphate (CaP) mineralized PLGA nanoparticles. This reinforced vaccine shows better stimulation of both humoral and cellular immune responses than aluminum-adjuvanted vaccines when exposed to dual TLR agonists.

Tumor development and metastasis are intimately associated with the tumor microenvironment (TME), and it is difficult for vector-restricted drugs to act on the TME for long-term cancer immunotherapy. Virus-like particles (VLPs) are nanocage structures self-assembled from nucleic acid free viral proteins. Most VLPs range from 20–200 nm in diameter and can naturally drain into lymph nodes to induce robust humoral immunity. As natural nucleic acid nanocarriers, their surfaces can also be genetically or chemically modified to achieve functions such as TME targeting. This review focuses on the design ideas of VLP as nanocarriers and the progress of their research in regulating TME.

Nowadays, the overuse of antibiotics in cow breeding is a common issue worldwide. Real-time monitoring is critical for antibiotic control of dairy products. Herein, we report a rapid detection method for the duplex detection of two beta-lactam antibiotics (cephalexin and ampicillin) in milk powder using lateral flow (LF) combined with surface-enhanced Raman spectroscopy (SERS). The duplex detection was accomplished using a single test line loaded with two antigens targeting the two corresponding antibody-gold-Raman reporter conjugates. The obtained SERS spectra contributed by the Raman reporter labeled to the two antibodies were analyzed using both peak height method and multiple linear regression (MLR). A good regression fitting was achieved by these two methods (R2 = 0.99 and 0.98, respectively). The limit of detection (LOD) was 10−4 ng/mL for both peak height method and MRL. This study indicated that LF-SERS is a good candidate for real-time multiplex and quantitative analysis for antibiotics in dairy products.

As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid–base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells. This treatment is called ion interference therapy (IIT). Although some molecular carriers of ions have been developed for intracellular ion delivery, inorganic nanoparticles are widely used in ion interference therapy because of their higher ion delivery ability and higher biocompatibility compared with molecular carriers. This article reviewed the recent development of IIT based on inorganic nanoparticles and summarized the advantages and disadvantages of this treatment and the challenges of future development, hoping to provide a reference for future research.

At present, vaccination is the only effective and low-cost way to prevent and treat COVID-19. At present, the vaccines vaccinated on a large scale are inactivated COVID-19 vaccines, which have the risk of insufficient immunogenicity, low neutralizing antibody production level and short maintenance time, and incomplete pathogen inactivation leading to adverse reactions. The recombinant subunit vaccine can effectively overcome the problem of poor safety of inactivated virus vaccines by using immune epitope proteins or peptides as recognition epitopes, and with the assistance of appropriate adjuvants, it can produce high levels of neutralizing antibodies and maintain good immune memory. This paper will review the application of recombinant protein antigen of COVID-19 virus and various adjuvants, and prospect the future application of recombinant protein vaccine.

在膀胱功能障碍性疾病及膀胱肿瘤治疗中,纳米技术作为一项新兴的治疗策略,因其有效的尺寸效应、可靶向修饰等优势,为药物体内高效递送提供了广阔的应用前景.作为治疗膀胱疾病的有效给药途径,膀胱内灌注的疗效优于全身给药途径.然而,周期性排尿会冲洗掉灌注入的药物,导致药物的持续作用时间减少;膀胱通透性屏障的存在也限制了药物向炎症部位及肿瘤组织的渗透.因此,开发新型纳米给药系统至关重要.该研究综述了纳米递药系统治疗膀胱功能障碍性疾病和膀胱肿瘤的相关研究,以期为今后改进临床治疗手段提供更多的思路和方法.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response. Thus, the combination of immunotherapy and LTD methods will be a promising approach to improve immune efficiency for cancer treatment. Herein, a nanobiotechnology platform to achieve high-precision LTD for systemic cancer immunotherapy has been successfully constructed. Possessing radio-sensitizing and photothermal properties, the engineered immunoadjuvant-loaded nanoplatform, which could precisely induce radiotherapy (RT)/photothermal therapy (PTT) to eliminate local tumor and meanwhile lead to the release of tumor-derived protein antigens (TDPAs), has been facilely fabricated by commercialized SPG membrane emulsification technology. Further on, the TDPAs could be captured and form personal nanovaccines in situ to serve as both reservoirs of antigen and carriers of immunoadjuvant, which can effectively improve the immune response. The investigations suggest that the combination of RT/PTT and improved immunotherapy using adjuvant-encapsulated antigen-capturing nanoparticles holds tremendous promise in cancer treatments.