CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Jian Wu,Zhiqiang Chen,Haojie Shang,Yonghua Tong,Wen Deng,Yu He,Xiaozhuo Ba,Zichen Zhong,Yongke Bai,Tao Ye,Xiaoqi Yang,Kehua Jiang,Yijing Liu,Kun Tang
Limited lymphocyte infiltration and insufficient tumor immunogenicity remain major challenges for effective immunotherapy in bladder cancer, particularly in immunologically “cold” tumors with a highly suppressive immune microenvironment. Effective activation of the innate immune system is critical for initiating a robust adaptive anti-tumor immune response, primarily mediated by dendritic cells (DCs). Here, we designed genetically engineered hybrid membrane-coated nanoparticles (HM-MPS NPs) with excellent photothermal stability, tumor-targeting capability, and biocompatibility. HM-MPS NPs demonstrated significant tumor-suppressive effects in multiple preclinical models, including murine subcutaneous, orthotopic, and distant bladder tumor models. By combining photothermal therapy (PTT), a STING agonist (SR717), and antigen presentation, HM-MPS NPs achieve triple activation of DCs, leading to enhanced T-cell activation and a remodeled immune microenvironment. Furthermore, HM-MPS NPs synergize effectively with anti-PD-1 therapy, amplifying immunogenic cell death (ICD) and overcoming immune suppression within the tumor microenvironment. This strategy significantly boosts tumor immunogenicity and enhances anti-tumor immune responses, offering a promising approach for bladder cancer treatment.
研究领域:
肿瘤学
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免疫学
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纳米医学
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DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Guoqing Zhong,Yali Miao,Jielong Zhou,Yijie He,Wenjie Yang,Chongquan Huang,Yunhui Zhang,Jin Xiao,Bingqing Bai,Jiaqi Zhou,Renshan Li,Tiantian Wei,Yu Zhang,Shi Cheng
Approximately half of lung cancer patients experience bone metastasis, leading to bone loss, fracture, and other skeletal-related events. Although immunotherapies have significantly advanced the therapeutic landscape for lung cancer, bone metastases have an immunologically "cold" microenvironment, representing a challenging obstacle when treating lung cancer. The combination of immunotherapy and photothermal therapy (PTT) for treating tumor-induced bone defects holds promise for enhancing the efficacy of local tumor ablation and inhibiting tumor recurrence and metastasis through activating systemic immune responses. Herein, we developed an injectable hydrogel-based photothermal immunotherapy system (BP@Gel-CD[SA] hydrogel) incorporating STING agonists (SA) and black phosphorus nanosheets (BPNSs) for high-efficiency tumor elimination, immune activation, and bone regeneration. The photothermal and photodynamic activities of BPNSs induce hyperthermia and ROS-mediated apoptosis of tumor cells. Meanwhile, SA loaded into the nano-boxes in BP@Gel-CD[SA] hydrogel by host-guest interaction significantly activates the cGas-STING pathway. It stimulates immunogenic cell death (ICD), synergistically promoting immune cell infiltration. Single-cell RNA sequence analysis confirms the modulation of the tumor microenvironment (TME) through the PTT-mediated ICD effect and the transactivation of the cGAS-STING pathway in immune cells of the TME. More importantly, the system can significantly inhibit the growth of distant tumors via systemic immune activation and elicit long-term immune memory in addition to tumor eradication. In the long term, this hydrogel system can promote the formation of new bone at sites of tumor-induced bone destruction, improving bone strength in the affected area. Collectively, this strategy provides an effective and safe option for treating lung cancer bone metastases.
研究领域:
肿瘤学
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生物材料学
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免疫学
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DOI
PubMed
高影响因子
Nanoscale
·
2025
·
IF 5.1
Jingxian Yang,Mengyao Chen,Ruihao Li,Yanting Sun,Pingting Ye,Kang Fang,Chunhui Wang,Shuo Shi,Chunyan Dong
The exclusion of immune cells from the tumor can limit the effectiveness of the immunotherapy in triple negative breast cancer (TNBC). The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway plays a crucial role in priming adaptive anti-tumor immunity through type I interferons (IFNs) production, facilitating the maturation of dendritic cells (DCs) and the function of T cells. Although the increased programmed death-ligand 1 (PD-L1) expression upon STING activation is favorable for amplifying the efficacy of immune checkpoint inhibitors (ICIs) and realizing combination therapy, the penetration barrier remains a major obstacle. Herein, we fabricated a smart-responsive nanosystem (B&V@ZB-MCL) by integrating the extracellular matrix (ECM)-degrading drug losartan with STING agonist (Vadimezan, abbreviated as Vad) and PD-L1 inhibitor (BMS-1). Losartan was first released in the acidic tumor microenvironment to overcome physical barrier, enhancing the penetration of immunotherapeutic components. Under the triggering of 1O2 generated by photosensitizer (Ce6), the reactive oxygen species (ROS)-sensitive degradation of nanocore ensure the site-directed release of Vad and BMS-1. The released Vad and damaged tumor DNA activated immune responses through cGAS-STING pathway, while the elevated expression level of PD-L1 promoted the anti-tumor effect of BMS-1. Significant degradation of collagen fibers, restoration in immune effector cells, and lower tumor volume were observed in this integrating triple drug sequential therapy, which provides a promising prospect for the TNBC treatment.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Bin Chen,Hang Li,Hong Zhang,Junyan Xu,Shuofu Liang,Ghazal Shokraneh,Hecheng Ma,Gang Wang,Junhao Lin,Zhijian Wei
Background Diabetic wound, a severe complication of diabetes mellitus, are characterized by chronic inflammation, impaired angiogenesis, and prolonged wound healing. As a somatostatin analog, octreotide (Oct) has been previously found to promote wound healing. However, its application is limited by its low stability and susceptibility to enzymatic degradation. Methods Octreotide was incorporated into a dual-network hydrogel (CS-PBA/PVA/PA) with a 3D porous structure using a one-pot method to form CPP@Oct. Its physicochemical properties, drug release behavior, and biological effects were evaluated in vitro and in vivo. Network pharmacology, Western blotting, immunohistochemistry, and animal models (db/db mice and diabetic rats) were used to investigate the mechanisms and therapeutic effects of CPP@Oct. Results The unique design of the CPP@Oct double-network hydrogel demonstrates exceptional swelling capacity, self-healing properties, and controlled drug release characteristics in high-glucose environments. It significantly reduced inflammatory markers and reactive oxygen species (ROS), promoted angiogenesis (increased CD31, VEGF), and enhanced mitochondrial function. In animal models, CPP@Oct accelerated wound closure, increased collagen deposition, and improved vascular density. Mechanistically, it suppressed the cGAS-STING pathway, alleviating inflammation and promoting tissue repair. Conclusion CPP@Oct hydrogel offers a promising therapeutic strategy for diabetic wound by simultaneously addressing inflammation, angiogenesis, and tissue repair through cGAS-STING pathway inhibition. Its dual-network design provides a versatile platform for targeted drug delivery in wound healing applications.
研究领域:
生物医学工程
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伤口愈合
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药物递送
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分子生物学
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糖尿病研究
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2026
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IF 8.2
Yanfang Cheng,Yebi Qin,Wenhui Zhu,Weirong Yao,Hang Zou,Bairong He,Lizhi Yan,Lei Zheng
Photoimmunotherapy is limited by inadequate dendritic cells (DCs) antigen presentation and cytotoxic T lymphocytes (CTLs) dysfunction. Innate immune activation can potentiate DCs maturation and restore CTLs function, augmenting photoimmunotherapy efficiency. Herein, we developed a biomimetic gold nanorod-core/mesoporous manganese dioxide (MnO2)-shell nanoagonist (denoted as m@AMCR) loaded with chlorin e6 and rapamycin (Rap) to synergize photodynamic therapy (PDT)/photothermal therapy (PTT) with cGAS-STING pathway activation for enhanced tumor treatment. Tumor cell membrane biomimetic camouflage conferred m@AMCR with self-targeting ability toward homologous cancer cells. Subsequently, intratumoral glutathione triggered MnO2 decomposition to release Rap. Rap augmented PDT/PTT by suppressing hypoxia-inducible factor-1α and heat shock protein 70 expression while downregulating matrix metalloproteinase-2 to inhibit tumor metastasis. Concurrently, the released Mn2+ activated the cGAS-STING pathway, promoting DCs maturation and CTLs infiltration. Finally, the combination of photoimmunotherapy-induced immunogenic cell death and cGAS-STING activation potently suppressed primary tumor growth and lung metastases. Overall, this biomimetic self-augmenting nanoagonist established a paradigm for tumor immunotherapy by integrating photoimmunotherapy with cGAS-STING-mediated innate immune activation.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Pan Zhang,Minglun Liu,Lei Huang,Zijie Zhao,Qianqian Zhang,Yunhao Li,Yuncong Chen,Lili Liang
Triple-negative breast cancer (TNBC) frequently exhibits profound chemoresistance and a highly immunosuppressive tumor microenvironment (TME), leading to suboptimal clinical outcomes with high risks of early recurrence and distant metastasis. Existing monotherapies remain inadequate in disrupting these therapeutic barriers. To overcome the aforementioned obstacles, we developed a spatiotemporally regulated organelle-targeted nanoplatform, IR820-GEM@MIL101 (IGM), Its design aims to achieve precise mitochondrial intervention and coordinate cGAS–STING-mediated immune activation. This design relies on EPR-mediated passive targeting to achieve preferential tumor accumulation, allowing IGM to accumulate specifically in tumor tissues and trigger a series of reactions in response to endogenous stimuli (acidic pH and elevated glutathione) in synergy with exogenous near-infrared laser activation, enabling controlled drug release. The platform efficiently eliminates tumor cells by inducing multiple modes of cell death, including pyroptosis, ferroptosis, and apoptosis, while simultaneously triggering immunogenic cell death (ICD) and activating the cGAS–STING pathway. This dual immunostimulatory strategy effectively converts “cold” tumors into “hot” tumors. In a bilateral tumor model, IGM treatment increased CD8 + T-cell infiltration in distal tumors by 94% and achieved a tumor inhibition rate of 92.7% in distant lesions. This work shifts the therapeutic focus from superficial multi-drug packaging to precise organelle-targeted intervention, providing a promising strategy for light-regulated combinatorial immunotherapy against aggressive malignancies.
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Wang Huan-Hui,Nan Long-Yi,Zheng Yan,Guo Jianpeng
Sonodynamic therapy (SDT) offers deep tissue penetration and noninvasive tumor treatment, yet its efficacy remains limited by inadequate reactive oxygen species (ROS) generation and an immunosuppressive tumor microenvironment (TME). In this work, we developed a porphyrin-based bimetallic nanoplatform by integrating Fe and Mn centers within a structurally ordered metal-organic framework (MOF), followed by surface modification with the tumor-homing peptide CRGDK to achieve active targeting. The rationally engineered Mn-Fe(TCPP) MOF exhibits a spatially confined configuration that minimizes π-π aggregation of porphyrins enhancing ROS production under ultrasound (US). Meanwhile, Fe 3+ and Mn 2+ are released in the mildly acidic TME. The Fe 3+ catalyzes Fenton-like reactions to generate abundant •OH radicals, leading to glutathione (GSH) depletion, glutathione peroxidase-4 (GPX4) inhibition, and triggers ferroptosis. Simultaneously, Mn 2+ and ROS inflict mitochondrial damage and cause cytosolic double-stranded DNA (dsDNA) leakage, thereby activating the cGAS-STING signaling pathway and amplifying type I interferon (IFN-I) responses. This dual immunometabolic modulation induces immunogenic cell death (ICD), promotes dendritic cells (DCs) maturation, and strengthens adaptive antitumor immunity. Overall, this study presents a concise strategy coupling ferroptosis induction with innate-immune activation through a porphyrinic bimetallic MOF, offering a promising direction for SDT-based immunotherapy against hard-to-treat tumors. Graphical The alternative text for this image may have been generated using AI.
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DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·649
·
IF 6.9
Congyi Zhang,Haotian Wu,Xiaotong Chen,Wenze Yin,Shizhuan Huang,Dixiang Wen,Xueting Song,Xiaoyan Xu,Changmei Zhang,Sheng Tai
Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy.Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release.Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment.Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance.
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DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Linhao Jing,Shuaijun Zhao,Chenguang Sun,Fangfang Cui,Yaning Xia,Yupeng Shi,Weijie Wang
Immunotherapy has reshaped cancer treatment, yet its efficacy in many solid tumors remains limited by an immunosuppressive microenvironment and insufficient antigen presentation. As a central gatekeeper of antitumor immunity, the cGAS-STING pathway represents a key axis for converting tumor-intrinsic stress into productive immune priming. Here, we propose an integrated strategy that couples immunogenic tumor cell death with tumor-restricted cGAS-STING activation and adjuvant-amplified innate signaling. Cuproptosis, a recently identified copper-dependent cell-death program, can act as an endogenous trigger of tumor-intrinsic cGAS-STING activation, providing a promising avenue to link cytotoxicity with immune stimulation. We engineered a biomimetic, tumor-responsive nanoplatform (Cu-R837@CM) by co-assembling Cu 2+ with the TLR7 agonist R837 and cloaking the core with homologous tumor cell membranes to enhance tumor targeting and intratumoral retention. In vitro, Cu-R837@CM released Cu 2+ under acidic conditions, inducing glutathione depletion and ROS accumulation, promoting DLAT aggregation and mitochondrial dysfunction, increasing intracellular 2′3′-cGAMP, and activating cGAS-STING signaling. Concurrently, R837 enhanced dendritic-cell maturation and cytokine production, thereby improving antigen presentation. In vivo, Cu-R837@CM markedly inhibited tumor growth, increased CD4 + /CD8 + T-cell infiltration, and remodeled the tumor immune microenvironment toward an antitumor phenotype. Notably, combining Cu-R837@CM with PD-L1 blockade achieved complete tumor regression and significantly prolonged survival. Collectively, Cu-R837@CM offers a clinically translatable nanoadjuvant paradigm that integrates cuproptosis-driven cGAS-STING activation with TLR7 co-stimulation for hepatocellular carcinoma immunotherapy.
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2026
·
IF 10.4
Qiuyu Wang,Qiwei Chen,Di Li,Xueke Jia,Jie Ren,Hezhen Xie,Fei Hu,Xiaoxue Wang,Xueyang Zhang
Antibacterial treatment reduces residual bacterial burden in periodontitis, but rapid bacterial killing and lysis can also increase exposure to danger signals such as bacterial DNA (bDNA), which can contribute to cGAS–STING-associated innate immune activation. To address this bactericidal stress-associated inflammation, we constructed a ROS-responsive coordination nanosystem, CPLEA, in which the STING inhibitor C-176 was incorporated during Ag⁺-mediated co-assembly of epicatechin and the sulfur-containing PEG ligand methoxy poly(ethylene glycol)–dihydrolipoic acid (mPEG-DHLA), thereby integrating antibacterial activity with the regulation of post-bactericidal STING-associated inflammation. Without compromising bacterial killing, CPLEA promoted C-176 release under oxidative conditions, and the release profile showed temporal overlap with bacterial killing and bDNA exposure. CPLEA attenuated the inflammatory state of macrophages and relieved the suppression of hPDLSC osteogenic differentiation by macrophage-conditioned medium. Transcriptomic analysis indicated downregulation of cytosolic DNA sensing, NF-κB, IL-17, and osteoclast differentiation programs. In a ligature-induced mouse model of periodontitis, CPLEA attenuated local inflammation and TRAP-positive osteoclast accumulation and reduced alveolar bone loss. Collectively, these findings support bactericidal stress-associated STING signaling as a relevant target during local antibacterial treatment of periodontitis and position CPLEA as a feasible materials-based approach for this purpose. Statement of significance Periodontitis treatment often requires additional antimicrobial control after mechanical debridement, yet rapid bacterial killing and lysis can increase the exposure of bacteria-derived danger signals and thereby sustain host inflammatory responses. This study develops an oxidation-responsive coordination nanoplatform that integrates antibacterial activity with STING-targeted immunomodulation. By incorporating the STING inhibitor C-176 into an Ag⁺-mediated coordination system, CPLEA enables oxidation-promoted C-176 release within a temporal window overlapping bacterial killing and bacterial DNA exposure. The study further demonstrates that early C-176 intervention more effectively regulates STING-associated inflammatory signaling than delayed intervention. CPLEA attenuated macrophage inflammatory responses, alleviated inflammation-associated suppression of periodontal ligament stem cell osteogenic differentiation, and reduced inflammation, osteoclast accumulation, and alveolar bone loss in experimental periodontitis. These findings highlight the importance of immunomodulator availability during the early phase of bactericidal treatment and provide a biomaterials strategy for integrating residual bacterial control with local host modulation. Download: Download high-res image (214KB) Download: Download full-size image
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高影响因子
Nature Metabolism
·
2026
·Vol. 8
·期 8
·1713-1729
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IF 27.5
Deng Jiangming,Meng Wen,Yang Yuanqin,Xiao Ting,Jin Zhangliu,Wang Jing,Li Qing-xin,Xie Lingxiang,Hu Jingyi,Song Rong,Hu Yibo,Chu Yi,Li Qing,Jin Ping,Wang Zheng,Wu Irene XY,Liu Feng,Xiao Yang
The gut constantly interacts with both pathogens and dietary signals, but how it balances immune and metabolic responses remains unclear. Here we show that intestinal cGAS, a key DNA sensor, acts as a regulator linking gut immunity to whole-body metabolism. We show that cGAS signalling is activated in the intestines of humans and male mice with obesity, leading to increased type I interferon production and heightened immune activity in intestinal cells. Strikingly, deleting cGAS specifically in intestinal epithelial cells enhances energy expenditure, protects against diet-induced obesity and improves metabolic health. These effects depend on the gut microbiota, particularly Lactobacillus murinus and its metabolite indole-3-acetic acid (IAA), which promotes adipose thermogenesis. Our findings position intestinal cGAS as a key driver of obesity through gut-to-fat signalling and suggest that targeting the intestinal cGAS–microbiota IAA axis could offer promising strategies to combat obesity and related metabolic diseases.
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高影响因子
Theranostics
·
2025
·Vol. 15
·期 14
·6919
·
IF 13.3
Wen Hu,Xiaohong Hong,Xinyu Zhang,Hongfan Chen,Xin Wen,Feng Lin,Jingwen Liu,Chenfenglin Yang,Binglin Cheng,Hanrui Zhu,Moting Zhang,Ruzhen Chen,Tingting Peng,Xinran Tang
Background: Radiotherapy (RT) often activates the cyclic GMP-AMP synthase (cGAS) stimulator of interferon response cGAMP interactor (STING) signaling pathway and induces systemic immunotherapy effects by triggering immunogenic cell death (ICD) in various solid tumors. However, RT-induced ICD usually falls short in eradicating distant tumors because of moderate anti-tumor immune responses. Methods: In this study, Mn-ZIF-8 nanoparticles and microneedles were prepared, and their physical and chemical properties were characterized. Subsequently, in vitro experiments using B16 and A375 cutaneous melanoma cell lines were conducted to investigate the radiosensitivity characteristics of Mn-ZIF-8 and its mechanism for enhancing RT efficacy. Moreover, mouse models bearing primary and distant B16 cutaneous melanoma were established to clarify the immunomodulatory effect and antitumor efficacy of Mn-ZIF-8 microneedles when combined with RT and immunotherapy. Results: A percutaneous delivery method based on soluble microneedles (MNs) with Mn 2+ -loaded, X-ray-responsive zeolite imidazolate frame-8 (ZIF-8) was designed. This microneedle-based drug delivery system, combined with RT, promoted the radiosensitivity of cutaneous melanoma and reinforces ICD by augmenting STING pathway activation. Furthermore, after X-ray irradiation, Mn-ZIF-8 MNs continuously released Mn 2+ in the tumor to enhance cGAS-STING activation. This promoted dendritic cell maturation and antigen presentation, and potentiated a T cell mediated immune response. Thus, the local and systemic immune effects induced by RT were amplified when combined with immune checkpoint inhibitors. Conclusion: The microneedle patches with X-ray-responsive, rapid dissolution and controlled release abilities have the potential to enhance the radioimmunotherapy efficacy for cutaneous melanoma.
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PubMed
高影响因子
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