Adv Healthc Mater. 2025 Mar;14(6):e2403865. doi: 10.1002/adhm.202403865. Epub 2025 Jan 2. Coacervate-Derived Assembly of Poly(ethylene glycol) Nanoparticles for Combinational Tumor Therapy Abstract Coacervates have garnered significant attention as potential drug carriers. However, the instability resulting from their intrinsic membrane-free nature restricts the application of coacervates in drug delivery. Herein, the engineering of poly(ethylene glycol) nanoparticles (PEG NPs) is reported using coacervates composed of PEG and polyphenols as the templates, where PEG is subsequently cross-linked based on different chemistries (e.g., thiol-disulfide exchange, click chemistry, and Schiff base reaction). The reported assembly strategy avoids the template removal process and the resultant PEG NPs exhibit excellent stability in the physiological environment compared to coacervates. The presence of polyphenols in PEG NPs enables the loading of various cargos including metal ions (i.e., Ru, Gd, Mn, Fe) and drug molecules (i.e., doxorubicin), which demonstrates their promise in magnetic resonance imaging and combinational tumor therapy. This work provides a promising strategy to promote the development of coacervate-derived NPs as a drug delivery system for biomedical applications. Keywords: coacervates; drug delivery; nanoparticles; poly(ethylene glycol); self‐assembly. Product: 8-arm PEG-NH2HCl (HG)

Biomaterials. 2026 Feb:325:123568. doi: 10.1016/j.biomaterials.2025.123568. Epub 2025 Jul 19. Chrono-controlled hydrogel platform orchestrates metabolic reprogramming and cuproptosis-driven immune activation against triple-negative breast cancer Abstract Triple-negative breast cancer (TNBC) poses significant therapeutic challenges due to its metabolic plasticity and immunosuppressive microenvironment. In this study, we present a sequential drug release hydrogel system (SeqGel) that reprograms tumor metabolism and modulates the immune landscape to suppress TNBC growth and metastasis. The poly(ethylene glycol)-based injectable hydrogel system could enable tunable biodegradation within 48 h to ensure repeated peritumoral administration and localized controlled drug release. Specifically, water-soluble small molecular dichloroacetate is rapidly released to redirect tumor cell metabolism from glycolysis to oxidative phosphorylation, thereby reducing lactic acid accumulation, restricting glucose uptake, and enhancing the susceptibility of cancer cells to mitochondrial damage. This is followed by the sustained release of pH-sensitive, copper complex-loaded polymeric nanoparticles PED@tCu, which facilitates efficient intracellular delivery and targeted mitochondrial localization, specifically impairing the function of complex II. Mechanistically, the ordered metabolic intervention enhances antitumor immunity by activating the AMPK pathway, promoting PD-L1 degradation, and upregulating MHC I to improve antigen presentation. In 4T1 subcutaneous tumor models, SeqGel effectively suppressed tumor growth and markedly reduced lung and lymph node metastases by promoting CD8+ T cell infiltration and depleting regulatory T cells. This study establishes a paradigm for metabolic-immune synergy, offering a promising strategy for targeting aggressive cancers through chrono-metabolic immunotherapy. Keywords: Hydrogel; Immunogenic cuproptosis; Immunotherapy; Metabolic reprogramming; Sequential drug release. Product: 4-arm PEG-SG

Bioact Mater. 2025 Jul 5:52:878-895. doi: 10.1016/j.bioactmat.2025.06.007. eCollection 2025 Oct. Catalyst-modulated hydrogel dynamics for decoupling viscoelasticity and directing macrophage fate for diabetic wound healing Abstract Dynamic hydrogels can regulate immune responses, but decoupling bond exchange kinetics from static mechanical properties remains challenging. Here, we present a catalyst-mediated strategy to independently tune hydrogel network dynamics without altering crosslinking density or stiffness. A reversible acylhydrazone-based hydrogel system was constructed using lysozyme and PEG, with 4-amino-DL-phenylalanine (4a-Phe) as a catalyst to modulate bond exchange rates. This strategy enables effective decoupling of hydrogel viscoelasticity, allowing precise modulation of stress relaxation rates (τ1/2) from 50 to 15 min, while maintaining nearly identical storage moduli (G'). The impact of hydrogel network dynamics on macrophage behavior was systematically investigated. Hydrogels with enhanced network dynamics significantly activated the JAK/STAT signaling pathway, promoting macrophage M2 polarization. These immunomodulatory effects fostered a pro-regenerative microenvironment, enhancing granulation tissue formation, angiogenesis, and accelerating wound closure in a diabetic mouse model. These findings underscore the significant potential of dynamic hydrogels in materiobiology, offering a novel approach to bridging materials science with immunoregulatory regenerative medicine. Keywords: Diabetic wound healing; Dynamic hydrogel; Immunomodulation; Macrophage polarization; Stress relaxation. Product: 4-arm PEG-HZ

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