ACS Nano. 2025 Dec 16;19(49):41803-41815. doi: 10.1021/acsnano.5c15619. Epub 2025 Dec 4. Engineering of Metal-Organic Networks as Band-Aid for the Repair of Osteoporotic Bone Fractures Abstract The treatment of osteoporotic bone fractures remains a critical challenge due to the dysregulated bone remodeling microenvironment characterized by excessive osteoclastic resorption, impaired osteogenic differentiation, angiogenic dysfunction, and chronic inflammation. In this work, we engineered a metal-organic network as a bone repair "band-aid" by integrating poly(ethylene glycol)-alendronate (PEG-ALN) conjugates with bioactive epigallocatechin gallate (EGCG), zinc, and calcium ions into a multifunctional scaffold. This design leverages the synergistic effects of anti-inflammatory and antioxidant properties of EGCG with the balancing osteogenic and osteoclastic functions of ALN, zinc, and calcium ions. In vitro studies demonstrated that the band-aid significantly enhanced the proliferation and differentiation of osteoblasts while promoting endothelial cell migration and tubule formation, indicating the robust osteogenic and angiogenic potential. In vivo evaluations in an osteoporotic bone fracture model revealed accelerated bone regeneration and improved microvascularization while maintaining a balanced immune response to prevent chronic inflammation. Mechanistically, the band-aid modulated macrophage polarization toward a pro-regenerative M2 phenotype and suppressed excessive osteoclast activity, thereby restoring the osteogenic-osteoclastic equilibrium. This study not only provides a therapeutic implant for osteoporotic bone repair but also proposes a strategy for designing immunomodulatory scaffolds that target the pathological bone microenvironment. Keywords: bone repair; metal−organic networks; osteoporosis; polyphenols; tissue engineering. Product: 8-arm-PEG-NHS

J Phys Chem Lett. 2025 Apr 17;16(15):3874-3878. doi: 10.1021/acs.jpclett.5c00825. Epub 2025 Apr 10. Double-Helix Duality: Rods Bow, Toroids Wow in the Nuclease Arena Abstract Utilizing polyion complexation, the formation of rod-like DNA condensates is driven by the intrinsic rigidity of supramolecular plasmid DNA. Upon interaction with polycationic block copolymers of poly(ethylene glycol)-polylysine (PEG-PLys), these macromolecules undergo a regular self-folding process, during which double-stranded DNA (dsDNA) transitions into single-stranded DNA (ssDNA) at the kinked junctions. Our investigations, employing transmission electron microscopy (TEM), unprecedentedly reveal the absence of a PEG coating at these critical junctions, rendering them susceptible to nuclease degradation. This finding underscores the critical necessity for comprehensive PEG encapsulation in the engineering of robust gene delivery constructs. In stark contrast to the anisotropic rod-like condensates, our novel isotropic toroidal DNA condensates, characterized by comprehensive PEG shielding and a self-spooling mechanism that preserves dsDNA integrity, exhibit a marked enhancement in enzymatic stability (nearly 30-fold greater). Their favorable condensation process also confers superior transcriptional potential, positioning these toroidal condensates as promising platforms for the next generation of gene delivery systems. Product: mPEG-NH2

Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2406434121. doi: 10.1073/pnas.2406434121. Epub 2024 Oct 22. CXCL13 promotes broad immune responses induced by circular RNA vaccines Abstract Antibody responses induced by current vaccines for influenza and SARS-CoV-2 often lack robust cross-reactivity. As hubs where diverse immune cells converge and interact, the alterations in the immune microenvironment within lymph nodes (LNs) are intricately linked to immune responses. Herein, we designed a lipid nanoparticle (LNP) loaded with circular RNA (circRNA) and targeted to LNs, in which CXCL13 was directly integrated into antigen-encoding circRNA strands. We demonstrated that CXCL13 alters the transcriptomic profiles of LNs, especially the upregulation of IL-21 and IL-4. Meanwhile, CXCL13 promotes the formation of germinal center and elicits robust antigen-specific T cell responses. With the codelivery of CXCL13 and the antigen, CXCL13 enhances cross-reactive antibodies against influenza virus and SARS-CoV-2, achieving protection against both homologous and heterologous influenza virus challenges in a mouse model. Notably, the targeted modification of LNP surfaces with antibodies helps address some of the challenges associated with lyophilized LNP vaccines, which is crucial for the long-term storage of LNP-circRNA vaccines. Overall, the circRNA-based antigen-CXCL13 coexpression system developed herein provides a simple and robust platform that enhances the magnitude and breadth of antibody responses against multiple viral glycoproteins, highlighting the potential utility of CXCL13 in inducing broad immune responses. Keywords: CXCL13; SARS-CoV-2; broadly cross-reactive antibodies; circRNA vaccine; influenza virus. Product: SM-102

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