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Objective Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high‐fat and high‐sugar (HFHS) diet. However, its effect and mechanism remain unclear. Materials and methods RNA‐Seq was used to detect the differentially expressed genes among each group. HFHS‐induced POF mouse model was generated and injected with siRNA using Poly (lactic‐co‐glycolic acid) (PLGA) as a carrier. Results RNA‐Seq suggested that 5TP promoted the expression of Yin Yang 2 (YY2) in mouse ovarian granulosa cell (mOGC) of HFHS‐POF mice. Luciferase reporter assay indicated that 5TP promoted the binding of YY2 to the specific sequence C(C/T)AT(G/C)(G/T) on the Lin28A promoter and promoted Lin28A transcription and expression. We continuously injected PLGA‐cross‐linked siRNA nanoparticles targeting YY2 into HFHS‐POF mice (siYY2@PLGA), which significantly reduced the therapeutic effect of 5TP. siYY2@PLGA injection also significantly attenuated the upregulation of Lin28a expression in mOGCs induced by 5TP and enhanced the expression of let‐7 family microRNAs, thereby inhibiting the proliferation and division of mOGCs. qPCR results showed that there was a significant difference in the expression levels of exosome‐derived Yy2 mRNAs between POF patients and normal women, and that there was a specific correlation between the expression level of exosome‐derived Yy2 and the peripheral concentrations of the blood hormones pregnenolone, progesterone and oestradiol. Conclusions Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibits the activity of let‐7 family microRNAs and alleviates the ageing of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice. Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibit the activity of let‐7 family microRNAs, and alleviate the aging of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice.

[This corrects the article DOI: 10.3389/fimmu.2025.1665710.].

Yong Chong Cao polysaccharides (CSPs) are extracted from Cordyceps militaris which has a wide range of pharmacological effects, especially in immune regulation. However, CSPs face certain drawbacks, including rapid metabolism and poor bioavailability, which hinder their use. The objective of this research was to enhance the preparation parameters of polyetherimide (PEI)-modified poly lactic-co-glycolic acid (PLGA), PLGA-PEI, which encapsulated CSP nanospheres using response surface methodology; investigate their properties; and evaluate their impact on RAW26.4 cells. The CSP-PLGA-PEI nanospheres were synthesized using the double emulsion solvent evaporation technique, and the best preparation conditions were determined to be a 0.5% concentration of poloxamer 188 (F68) (W/V), an organic phase (O) to water phase (W1) ratio (V/V) of 7:1, an external water (W2) to primary emulsion (PE) ratio (V/V) of 8:1, and a PLGA to PEI ratio (W/W) of 20:1, achieving a maximum encapsulation efficiency (EE) of 64.98%. The CSP-PLGA-PEI nanoparticles exhibited a nearly spherical form with a smooth exterior, were uniform in size, and demonstrated clear sustained release properties and consistent stability. Macrophages are important immune cells in innate immunity, and have remarkable polarization. CSP-PLGA-PEI nanospheres showed a good promoting effect on the activation of macrophages in our present study. In addition, CSP-PLGA-PEI nanospheres were much more effectively swallowed by RAW264.7 so that its promoting effect on immune regulation was higher than that of CSP. CSP-PLGA-PEI nanoparticles were able to effectively activate ROS signaling in zebrafish in vivo experiments and induce an immune response in their organism. Finally, CSP-PLGA-PEI nanospheres showed the potential to become a new type of immune enhancer or immune enhancement adjuvant. Graphical abstract

Bacterial infections constitute a threat to public health as antibiotics are becoming less effective due to the emergence of antimicrobial resistant strains and biofilm and persister formation. Antimicrobial peptides (AMPs) are considered excellent alternatives to antibiotics; however, they suffer from limitations related to their peptidic nature and possible toxicity. The present review critically evaluates the chemical characteristics and antibacterial effects of lipid and polymeric AMP delivery systems and coatings that offer the promise of enhancing the efficacy of AMPs, reducing their limitations and prolonging their half-life. Unfortunately, the antibacterial activities of these systems and coatings have mainly been evaluated in vitro against planktonic bacteria in less biologically relevant conditions, with only some studies focusing on the antibiofilm activities of the formulated AMPs and on the antibacterial effects in animal models. Further improvements of lipid and polymeric AMP delivery systems and coatings may involve the functionalization of these systems to better target the infections and an analysis of the antibacterial activities in biologically relevant environments. Based on the available data we proposed which polymeric AMP delivery system or coatings could be profitable for the treatment of the different hard-to-treat infections, such as bloodstream infections and catheter- or implant-related infections.

Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood-brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs' transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells in vitro through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.

Prion diseases, such as chronic wasting disease (CWD), are incurable, fatal neurodegenerative disorders. We have developed a recombinant dimeric deer prion protein (Ddi) vaccine against CWD that has shown promising immune responses when injected subcutaneously (s.c). While s.c injection is suitable for controlled conditions, oral administration is practical in wildlife. Herein, we have developed an oral vaccine utilizing poly lactic co-glycolic acid (PLGA) nanoparticles, co-encapsulating Ddi and oligodeoxynucleotide adjuvant (CpG) using double emulsion-solvent evaporation technique. Our results showed production of spherical PLGA nanoparticles with size of ~ 200–300 nm, an acceptable surface charge (− 14.2 ± 5.73 mV), and an encapsulation efficiency of approximately 70 and 30%, for Ddi and CpG, respectively. We administered the developed vaccine to FVB mice orally and subcutaneously, followed by ELISA assays of the sera and feces. Mice receiving the vaccine subcutaneously exhibited high antibody reactivities to the used antigen in their sera (100% positivity), with no detectable positive reactivity in their feces. However, those receiving the oral vaccine showed 60 and 80% positivity in sera and feces, respectively, indicating specific mucosal immunity. We also found specific T cell reactivity in mice immunized orally. This approach is paving the way for developing an oral vaccine against CWD.

Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.BackgroundSonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.MethodsIn this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.ResultsWhen low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.ConclusionThis study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.

Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, has shown remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin:Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL)-induced foam cell formation. Our studies demonstrated that Cur-Bio PLGA NPs (both ratios) maintained the cell viability in THP-1 monocyte-derived macrophages above 80% at all periods. The 1:0.2:10 ratio of Cur-Bio PLGA NPs at a concentration of 250 μg/mL illustrated an enhanced reduction in the relative cholesterol content in the THP-1-derived foam cells compared to the 1:1:10 ratio. Confocal microscopy analysis also revealed a reduction in macrophage-mediated foam cell formation when administered with both the ratios of Cur-Bio PLGA NPs. Relative fold change in the mRNA expression of the genes involved in the inflammatory pathways in the atherosclerotic process downregulated NF-κB, CCL2/MCP-1, CD-36, and STAT-3 activity while upregulating the SCAR-B1 expression when treated with the Cur-Bio PLGA NPs. This study thus highlights the importance of natural-based compounds towards the therapeutic intervention against atherosclerotic activity when administered as preventive medicine.

Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable biopolymer widely used in advanced drug delivery systems (DDSs) due to its biocompatibility, controllable degradation behavior, and tunable physicochemical properties. Its degradation into naturally metabolized lactic and glycolic acids makes PLGA particularly attractive for biomedical applications, positioning PLGA nanoparticles as versatile carriers that bridge material design and therapeutic delivery. In this context, electrospray (electrohydrodynamic atomization) has emerged as an innovative and scalable processing technique that enables precise control over nanoparticle size, morphology, and internal structure under mild conditions, which is particularly suitable for engineering biopolymer-based DDSs. This review provides a comprehensive overview of electrospray-fabricated PLGA nanoparticles, with emphasis on the relationship between processing conditions, polymer structure, and functional performance. The fundamental mechanisms governing drug release, including diffusion, polymer degradation, and their combined effects, are discussed in relation to PLGA properties. The influence of electrospray parameters on nanoparticle formation, morphology, and internal architecture is analyzed, highlighting how process–structure–property relationships can be tailored to achieve specific release profiles. Structural design strategies, including single-matrix, core–shell, and surface-functionalized nanoparticles, are further examined as approaches to enable controlled and sequential dual-DDSs. In addition, emerging modeling and computational approaches are briefly discussed as complementary tools for understanding and optimizing nanoparticle behavior. Challenges and technical problems, such as substrates for nanoparticle detachment, are discussed.

Tumor-specific neoantigens can be highly immunogenic, but their identification for each patient and the production of personalized cancer vaccines can be time-consuming and prohibitively expensive. In contrast, tumor-associated antigens are widely expressed and suitable as an off the shelf immunotherapy. Here, we developed a PLGA-based nanoparticle vaccine that contains both the immunogenic cancer germline antigen NY-ESO-1 and an α-GalCer analog IMM60, as a novel iNKT cell agonist and dendritic cell transactivator. Three peptide sequences (85–111, 117–143, and 157–165) derived from immunodominant regions of NY-ESO-1 were selected. These peptides have a wide HLA coverage and were efficiently processed and presented by dendritic cells via various HLA subtypes. Co-delivery of IMM60 enhanced CD4 and CD8 T cell responses and antibody levels against NY-ESO-1 in vivo . Moreover, the nanoparticles have negligible systemic toxicity in high doses, and they could be produced according to GMP guidelines. Together, we demonstrated the feasibility of producing a PLGA-based nanovaccine containing immunogenic peptides and an iNKT cell agonist, that is activating DCs to induce antigen-specific T cell responses.