Bioact Mater. 2026 May 28:65:76-93. doi: 10.1016/j.bioactmat.2026.05.035. eCollection 2026 Nov. An injectable tough hydrogel sealant enabling rapid hemostasis and promoting oral tissue regeneration Abstract Repair of oral soft-tissue injuries remains challenging due to the moist, bacteria-rich, and mechanically active oral environment, as well as the limitations of current sealants in wet adhesion, mechanical strength, biocompatibility, bioactivity, and sealing durability. Here, we report an injectable hydrogel sealant (PAG) composed of tetra-armed poly(ethylene glycol) succinimidyl succinate and amine-functionalized gelatin, which rapidly forms in situ via NHS-amine coupling without external triggers. The optimized formulation undergoes gelation within seconds and exhibits robust mechanical properties, as well as superior adhesive strength and burst pressure compared with commercial fibrin glue. PAG demonstrates excellent cytocompatibility, hemocompatibility, and biodegradability, while promoting fibroblast proliferation in vitro. In vivo, it enables rapid hemostasis within 3 s and effective tissue repair in an acute rat tongue perforation model, markedly outperforming suture, gelatin sponge, and fibrin glue controls. Moreover, PAG effectively protects early-stage wounds and accelerates repair in both rat and porcine oral mucosal defect models. Mechanistic studies indicate that PAG establishes a pro-regenerative microenvironment by attenuating excessive inflammation, enhancing angiogenesis, and promoting M2-dominant macrophage polarization. Collectively, these findings demonstrate that the engineered PAG hydrogel enables rapid, sutureless sealing and repair of oral soft-tissue wounds, highlighting its translational potential. Keywords: Adhesive hydrogel; Hemostasis; Medical sealants; Oral wound repair; Wound healing. Product: tetra-PEG-OH

Adv Sci (Weinh). 2026 Mar;13(17):e18356. doi: 10.1002/advs.202518356. Epub 2026 Jan 20. A Programmable Nanoreactor Orchestrates Cascade of DNA Sensing to Amplify cGAS-STING Activation for Cancer Immunotherapy Abstract The cGAS-STING pathway, a critical cytosolic DNA-sensing mechanism in innate immunity, holds significant promise for cancer immunotherapy. However, conventional DNA-damaging therapies lack tumor specificity and cause damage to normal tissue. Furthermore, dendritic cells (DCs), central to the STING-mediated immune response, exhibit extrinsic immunosuppression via inhibitory receptors such as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), which impairs DNA internalization and subsequent pathway activation. Herein, we engineered a telomere stress-induced nanoreactor composed of a pH-responsive zeolitic imidazolate framework-8 encapsulating telomerase-targeted 6-thio-2'-deoxyguanosine (6-thio-dG), with TIM-3 antibodies (αTIM-3) adsorbed onto its surface. Following accumulation in the tumor, the nanoreactor degrades within the acidic tumor microenvironment, releasing 6-thio-dG to induce tumor cell-specific telomeric DNA damage. Concurrently, the αTIM-3 blocks TIM-3 receptors on DCs, thereby enhancing their internalization of the released DNA. This dual-action strategy drives robust cGAS-STING activation, enhancing type I interferon production and DCs maturation. In murine models of immunogenic and poorly immunogenic tumors, the nanoreactor significantly suppresses tumor growth and prolongs survival. By coupling tumor-intrinsic telomere stress with DC-extrinsic checkpoint inhibition, this work establishes a precision platform for cGAS-STING pathway activation, presenting a promising therapeutic strategy for telomerase-positive malignancies. Keywords: TIM‐3 blockade; cGAS‐STING pathway; immunotherapy; nanoparticles; telomere stress. Product: 8-arm PEG-OH-40K

J Control Release. 2025 Oct 10:386:114126. doi: 10.1016/j.jconrel.2025.114126. Epub 2025 Aug 14. A novel ionizable lipid with comprehensive improvements in transfection potency, immune profile and safety of lipid nanoparticle Abstract Ionizable cationic lipid is critical for construction of lipid nanoparticles (LNPs) for mRNA delivery. Here, we reported the rational design and evaluation of FS01, a novel ionizable cationic lipid incorporating an ortho-butylphenyl-modified hydrophobic tail into a squaramide-based lipid headgroup architecture. Molecular dynamics simulations revealed that FS01 enhances mRNA stability through π-π stacking interactions between its aromatic tail and nucleobases aromatic rings, alongside hydrogen bonding via the squaramide headgroup. FS01-LNPs demonstrated smaller particle sizes (∼ 70 nm), high encapsulation efficiency (> 90 %), and superior mRNA delivery performance across intramuscular, subcutaneous, and intravenous routes in mice compared to FDA-approved lipids (Dlin-MC3-DMA, SM-102, ALC-0315). In prophylactic vaccine models (Varicella-zoster virus and Hepatitis B virus), FS01-LNP formulations elicited robust antigen-specific antibodies, memory B cells, and Th1-biased T cell responses, outperforming benchmark LNPs. Further, transcriptomic profiling and safety assessments demonstrated that FS01-LNP induced a well-balanced innate immune activation with minimal inflammation and liver toxicity, contrasting with the pronounced reactogenicity of Dlin-MC3-DMA and ALC-0315 LNPs. These findings highlighted FS01 as a promising ionizable lipid candidate for mRNA therapeutics, offering enhanced delivery efficiency, immunogenicity, and safety, with potential applications extending beyond vaccines to gene editing and protein replacement therapies. Keywords: Immunogenicity; Inflammation; Ionizable cationic lipid; Lipid nanoparticle; Reactogenicity; Π-π stacking interaction. Product: lipids for LNP

Bioconjug Chem. 2026 Jan 21;37(1):160-168. doi: 10.1021/acs.bioconjchem.5c00554. Epub 2026 Jan 10. "Zip-to-Cytosol": Glutathione-Cleavable Fluorinated Polyplexes Deliver siRNA at Single-Digit Nanomolar Dose with >90% Gene Silencing Abstract A fluorinated, disulfide-cross-linked polyplex platform (PFND) was developed for safe and potent cytosolic delivery of siRNA. Branched PEI (25 kDa) was first perfluoro-acylated to yield a membrane-zipper PF backbone, followed by orthogonal installation of azide (PF-N3) and strained alkyne (PF-DBCO) handles that undergo in situ copper-free click cross-linking in the presence of siRNA. The resulting 60 nm polyplexes (PDI < 0.1, ζ potential of approximately +22 mV) are stable in 10 mg mL-1 heparin (<5% siRNA leakage) yet quantitatively disassemble within 60 min in 10 mM glutathione, liberating the siRNA payloads. Compared with the commercial gold standard of Lipofectamine 3000, PFND delivers 2- to 3-fold more Cy5-siRNA into HeLa, HepG2, and MDA-MB-468 cells without detectable hemolysis or cytotoxicity. Consequently, 10 nM siGAPDH delivered by PFND silences approximately 93-98% of GAPDH mRNA across the three lines, remarkably outperforming gold-standard transfection reagents. The proposed reversible "locked-outside/labile-inside" design reconciles extracellular stability with rapid intracellular release, offering a valid tool for utilities of high-throughput siRNA screening or subject to be developed further for potential clinical translation of RNAi-based therapeutics. Product: NHS-PEG4-N3 Various Kingds And Grades Of Such Monodispersed Are Readily Avaliable| SINOPEG

J Exp Med. 2025 Sep 1;222(9):e20241454. doi: 10.1084/jem.20241454. Epub 2025 Jun 6. Membrane-IL12 adjuvant mRNA vaccine polarizes pre-effector T cells for optimized tumor control Abstract Conventional mRNA cancer vaccines can expand the quantity of tumor-specific CD8 T cells, but their effector function might be compromised. Specific cytokine signaling may enhance T cell differentiation for better tumor killing. We screened various cytokines and identified IL-12 as a potent adjuvant for mRNA vaccines, though with significant systemic toxicity. To balance efficacy and toxicity, we developed a membrane-tethered IL-12 (mtIL12) adjuvant mRNA vaccine. This design restricts mtIL12 expression to the surface of antigen-presenting cells, thereby selectively activating antigen-specific T cells without affecting bystander T or NK cells. mtIL12 adjuvant mRNA vaccination induced a unique pre-effector T cell subset that gives rise to highly responsive effector T cells, resulting in superior anti-tumor activity. Moreover, this approach overcame immune checkpoint therapy resistance and prevented cancer metastasis. Our study highlights that next-generation mRNA vaccines encoding membrane-tethered cytokine adjuvants can generate potent effector T cells, offering effective tumor control with reduced toxicity. Product: Wholesale Best Excipient For DNA/RNA Delivery,professional Excipient For DNA/RNA Delivery Suppliers

Bioact Mater. 2024 Jun 21:40:430-444. doi: 10.1016/j.bioactmat.2024.06.021. eCollection 2024 Oct. Kneadable dough-type hydrogel transforming from dynamic to rigid network to repair irregular bone defects Abstract Irregular bone defects, characterized by unpredictable size, shape, and depth, pose a major challenge to clinical treatment. Although various bone grafts are available, none can fully meet the repair needs of the defective area. Here, this study fabricates a dough-type hydrogel (DR-Net), in which the first dynamic network is generated by coordination between thiol groups and silver ions, thereby possessing kneadability to adapt to various irregular bone defects. The second rigid covalent network is formed through photocrosslinking, maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process. In vitro, an irregular alveolar bone defect is established in the fresh porcine mandible, and the dough-type hydrogel exhibits outstanding shape adaptability, perfectly matching the morphology of the bone defect. After photocuring, the storage modulus of the hydrogel increases 8.6 times, from 3.7 kPa (before irradiation) to 32 kPa (after irradiation). Furthermore, this hydrogel enables effective loading of P24 peptide, which potently accelerates bone repair in Sprague-Dawley (SD) rats with critical calvarial defects. Overall, the dough-type hydrogel with kneadability, space-maintaining capability, and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects. Keywords: Dough-type hydrogel; Dynamic network; Irregular bone defect; Kneadable; Rigid network. Product: Manufacturer Of PEG Derivative By Structure,Wholesale PEG Derivative By Structure

Pharmaceutics. 2025 Jan 24;17(2):157. doi: 10.3390/pharmaceutics17020157. Engineering Lipid Nanoparticles to Enhance Intracellular Delivery of Transforming Growth Factor-Beta siRNA (siTGF-β1) via Inhalation for Improving Pulmonary Fibrosis Post-Bleomycin Challenge Abstract Background/Objectives: Transforming Growth Factor-beta (TGFβ1) plays a core role in the process of pulmonary fibrosis (PF). The progression of pulmonary fibrosis can be alleviated by siRNA-based inhibiting TGF-β1. However, the limitations of naked siRNA lead to the failure of achieving therapeutic effect. This study aimed to design lipid nanoparticles (LNPs) that can deliver siTGF-β1 to the lungs for therapeutic purposes. Methods: The cytotoxicity and transfection assay in vitro were used to screen ionizable lipids (ILs). Design of Experiments (DOE) was used to obtain novel LNPs that can enhance resistance to atomization shear forces. Meanwhile, the impact of LNPs encapsulating siTGF-β1 (siTGFβ1-LNPs) on PF was investigated. Results: When DLin-DMA-MC3 (MC3) was used as the ILs, the lipid phase ratio was MC3:DSPC:DMG-PEG2000:cholesterol = 50:10:3:37, and N/P = 3.25; the siTGFβ1-LNPs could be stably delivered to the lungs via converting the siTGFβ1-LNPs solution into an aerosol (atomization). In vitro experiments have confirmed that siTGFβ1-LNPs have high safety, high encapsulation, and can promote cellular uptake and endosomal escape. In addition, siTGFβ1-LNPs significantly reduced inflammatory infiltration and attenuated deposition of extracellular matrix (ECM) and protected the lung tissue from the toxicity of bleomycin (BLM) without causing systemic toxicity. Conclusions: The siTGFβ1-LNPs can be effectively delivered to the lungs, resulting in the silencing of TGF-β1 mRNA and the inhibition of the epithelial-mesenchymal transition pathway, thereby delaying the process of PF, which provides a new method for the treatment and intervention of PF. Keywords: design of experiments (DOE); lipid nanoparticles (LNPs); pulmonary fibrosis (PF); siRNA delivery; transforming growth factor β1 (TGF-β1). Product: Wholesale Best Excipient For DNA/RNA Delivery,professional Excipient For DNA/RNA Delivery Suppliers

Molecules. 2017 Jul 15;22(7):1190. doi: 10.3390/molecules22071190. Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length Abstract A set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety (VG-PEG24-Chol) was found to be the best membrane fusion inhibitory peptide. Here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood mononuclear cells (PBMC). VG-PEG24-Chol showed the highest insertion rate and it was among the peptides that induced a larger change on the surface pressure of cholesterol rich membranes. This peptide also displayed a high affinity towards PBMC membranes. These data provide new information about the dynamics of peptide-membrane interactions of a specific group of antiviral peptides, known for their potential as multipotent paramyxovirus antivirals. Keywords: antiviral; cholesterol; membranes; paramyxoviruses; peptides. PEG Linker: Various Kingds And Grades Of Such Monodispersed Are Readily Avaliable| SINOPEG