Pharmaceutics
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2026
·Vol. 18
·期 6
·649
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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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CHEMICAL ENGINEERING JOURNAL
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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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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhisheng Luo,Ming Zhou,Ying Peng,Lu Hao,Jinhui Yang,Peng Liu,Shuo Hu
Current internal radioisotope therapy (RIT) struggles to achieve desirable treatment outcomes in solid tumors due to inadequate tumor-targeted delivery of radionuclides, and the hypoxic and immunosuppressive tumor microenvironment (TME). In this study, we rationally design and fabricate a radionuclide-labeled nanomedicine in which a tumor-targeting metal-phenolic network (MPN) is coated on the surface of 32 P-labeled biomineralized calcium phosphate (C-Ca 32 P) nanoparticles to realize targeted delivery of radionuclides and ABZI (a stimulator of interferon genes (STING) agonist). After internalization by tumor cells, such nanomedicine could alleviate hypoxia by oxygenation. Meanwhile, the pH-responsive decomposition of this nanomedicine triggers the liberation of radioactive 32 P, Mn 2+ and ABZI from acidic lysosomes, wherein ABZI and Mn 2+ synergistically potentiate STING signaling. Notably, the activation of STING pathway and in situ oxygenation sensitize tumor cells to 32 P-midiated internal radiation and arouse a type I interferons (IFNs)-related adaptive immune response, achieving obvious synergistic effect in eradicating orthotopic breast tumors. After combination with checkpoint blockade therapy, this nanomedicine could lead to amplified therapeutic effect and inhibition of distant tumor metastases. This study presents a promising strategy for internal radiation sensitization and immune activation, holding significant potential for enhanced radioisotope-immunotherapy.
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Materials Today Bio
·
2025
·
IF 10.2
Haitao Zeng,Huixiong Feng,Chong Zhang,Zhe Kang,Jianping Wu,Xingqi Zhao,Anfei Huang,Yanyang Xu,Yufeng Huang,Hongwen Xu,Ming Gong
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. While radiotherapy is an adjuvant treatment option for OS, particularly in cases of unresectable recurrent metastases, its efficacy remains limited. Enhancing radiosensitivity in OS cells is therefore crucial for improving treatment outcomes. Hafnium oxide, a known radiosensitizer, has demonstrated potential but its current formulation restricts its use to intratumoral administration, posing challenges for treating intraosseous tumors. The development of an intravenous formulation is thus highly desirable. Furthermore, radiotherapy resistance, driven by tumor hypoxia and an immunosuppressive microenvironment, further compromises its effectiveness. In this study, we synthesized hafnium-doped Prussian blue nanoparticles (HP) coated with a tannic acid-manganese metallophenol network (HPTM) to improve biocompatibility and enable intravenous administration. Following intravenous injection in a murine model of OS tibialis in situ tumors with lung metastases, HPTM effectively localized to the primary tumor. Within the acidic tumor microenvironment, manganese was released, activating the STING pathway and triggering anti-tumor immune responses. Moreover, near-infrared light irradiation of the Prussian blue component induced a photothermal effect, promoting apoptosis. Concurrently, under low-dose X-ray irradiation, HPTM augmented radiation energy deposition, generating reactive oxygen species and inducing DNA damage in tumor cells. This synergistic therapeutic approach significantly increased apoptosis in radiotherapy-resistant OS cells, reduced lung metastases, and suppressed primary tumor growth. These findings suggest a promising avenue for clinical translation, integrating radiosensitization, photothermal therapy, and STING pathway activation to overcome current limitations in OS radiotherapy.
研究领域:
肿瘤学
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放射生物学
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纳米医学
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Materials Today Bio
·
2025
·
IF 10.2
Zubair Hussain,Shanshan Gou,Xu Liu,Mengyu Li,Hanyue Zhang,Sumei Ren,Ruxia Han,Fangfang Liu,Xiaowen Zhou,Lu Qiu,Hongfei Wang,Zhenzhen Chen,Kangdong Liu
Immunotherapy has significantly advanced cancer treatment, but the tumor immune microenvironment (TIME) often remains immunosuppressive, limiting therapeutic efficacy. Tumor-associated macrophages (TAMs), particularly M2-like macrophages, play a crucial role in promoting tumor growth and immune evasion. Our study introduces a novel approach using dual-targeted ZrMOF/C@P nanoparticles, smartly engineered with cell membrane coating and enzyme responsiveness, to effectively modulate TAMs. These nanoparticles are synthesized and loaded with 2’, 3’-cGAMP, a STING agonist, and encapsulated in a peptide-expressed macrophage membrane (PMM) featuring Pep20, MMP2, and M2pep. In vitro , they activate the STING pathway in M2-like macrophages and reprogram them into M1-like macrophages. Smart ZrMOF/C@P is found to accumulate at the tumor even 72 hours post-injection. In CT26 and 4T1 tumor models show that smart ZrMOF/C@P not only suppresses tumor growth but also stimulates systemic immune responses. This is evidenced by a reduction in M2-like and an increase in M1-like macrophages, enhanced dendritic cell (DC) maturation, and increased tumor infiltration of CD4 + and CD8 + T cells, accompanied by elevated IFN-γ secretion. This innovative use of ZrMOF/C@P offers a promising strategy to transform the immunosuppressive TIME, presenting a versatile and effective treatment option for solid tumors, and novel avenue for non-CDN-STING agonists, facilitating systemic administration.
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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PubMed
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MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Kehong Dong,Mei Zhang,Ying Liu,Xintao Gao,Xiaochen Wu,Dayong Shi,Chuanlong Guo,Jing Wang
Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.
研究领域:
药剂学
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肝脏病学
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分子生物学
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Small Science
·
2025
·
IF 8.3
Yong Li,Youdong Zhou,Yinqiu Tan,Gang Deng
Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and high mortality. Early brain injury (EBI) is the main cause of high mortality and delayed neurological dysfunction in patients with SAH. Neuroinflammation is the important pathological processes of EBI.We prepared Silymarin nanoparticles (SIM NPs) through the solvent precipitation method and investigated their role in combating EBI following SAH in mice. We found that SIM NPs with a diameter of 150 nm have the strongest ability to cross the blood-brain barrier. SIM nanoparticles are spherical and contain irregular particles inside, which may be composed mainly of silibinin and assembled through hydrogen bonding. Further in vivo experiments showed that SIM NPs improved short-term neurological dysfunction in SAH mice, reduced cortical neural damage, and reduced EBI inflammation through the Nrf2/STING pathway. Finally, water maze experiments showed that SIM NPs can improve long-term memory and learning ability in SAH mice. Based on the above results, we conclude that silymarin nanoparticles can reduce EBI after SAH by inhibiting the Nrf2/STING pathway, inhibiting neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
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药理学
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分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xintao Gao,Tao Jiang,Xiaochen Wu,Yantao Li,Jun Xiao,Lin Long,Chuanlong Guo
Cervical cancer remains one of the leading causes of mortality among women, and immunotherapy targeting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway holds promise for its treatment. This study has developed nanoparticles based on fucoidan (Fu/CA NPs), successfully loading them with caffeic acid (CA) for application in cervical cancer therapy. In vitro experiments revealed that Fu/CA NPs significantly inhibited the proliferation of cervical cancer HeLa cells (by 65.73 ± 4.06 %) and induced apoptosis through the accumulation of reactive oxygen species and mitochondrial damage. Furthermore, treatment with Fu/CA NPs activated the cGAS-STING pathway, attributed to the cytoplasmic release of mitochondrial DNA (mtDNA) and the induction of DNA double-strand breaks (dsDNA) by Fu/CA NPs. In vivo results confirmed that Fu/CA NPs suppressed solid tumor growth (by 67.8 %), with even more pronounced antitumor effects observed when combined with cisplatin (96.5 %), a phenomenon also associated with the activation of the cGAS-STING pathway. Excitingly, the combination of Fu/CA NPs and cisplatin alleviated cisplatin-induced nephrotoxicity, as indicated by a decrease in blood urea nitrogen (BUN) by 53.27 % and serum creatinine (SCr) by 74.93 %. In summary, our research presents a potential therapeutic avenue for cervical cancer treatment, particularly highlighting the synergistic benefits of combining Fu/CA NPs with cisplatin.
研究领域:
肿瘤学
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药理学
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免疫学
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PubMed
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Materials Today Bio
·
2025
·
IF 10.2
Yong Fan,Zexuan Niu,Li Yin,Longtao Yao,Sheyuan Ding,Yu Tong,Jiao Wang,Zheping Hong,Jihang Chen,Qiong Zhang,Lichen Ji,Jiaxin Chen,Chen Xia,Qing Bi
Osteoarthritis (OA) is a progressive degenerative disorder which severely threatens the quality of life of older individuals. OA progression is closely related to heightened levels of mitochondrial reactive oxygen species (mtROS). Although nanozymes have a good ROS-scavenging effect, they cannot precisely scavenge mtROS because of the immune rejection of cell membranes, lysosomal escape, and the inability of conventional nanozymes to directly target mitochondria. Dual-target nanozymes were engineered to precisely scavenge mtROS in chondrocytes. We used chondrocyte membrane-camouflaged TPP-modified hollow Prussian blue nanozymes and subsequently encapsulated these nanozymes in a hybrid glycyrrhizic acid hydrogel. The therapeutic efficacy and underlying mechanisms were assessed in vitro and in vivo. The novel nanozymes enhanced cell selectivity, immune evasion capabilities, and mitochondrial targeting. The dual-targeted nanozymes exerted a pronounced therapeutic impact on inflammatory chondrocytes, mitigated mtDNA leakage by precisely scavenging mtROS, dampened cGAS-STING-NF-κB signaling, and enhanced chondrocyte function. The hybrid hydrogels also exhibited improved therapeutic outcomes. We confirmed the beneficial effects of the nanozyme-hydrogel combination on OA progression in mice. The nanozyme-hydrogel combination can reduce precisely scavenge mtROS in chondrocytes, avoiding the leakage of mtDNA and suppressing the cGAS-STING-NF-κB signaling pathway, thereby decreasing inflammatory responses and alleviate OA progression.
研究领域:
医学
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生物材料学
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分子生物学
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Science Advances
·
2025
·Vol. 11
·期 22
·
IF 12.5
Xiaoran Ding,Xiaoteng Jia,Hongming Yuan,Daxin Pang,Hualu Zhao,Peng Sun,Fangmeng Liu,Danming Chao,Meiying Xin,Caiyun Wang,Geyu Lu,Gordon Wallace
Metal ions are widely adopted to potentiate oxidative damage-induced immunogenic cell death (ICD) and regulate immune pathways. However, current ion delivery platforms lack precise administration over distribution and retention time within the tumor microenvironment, leading to high systemic toxicity and suboptimal therapeutic efficacy. Here, local electrochemical immunotherapy is developed by implanting a tumor microenvironment–activated Zn//MnO2 battery, which uses body fluid as an electrolyte and endogenous glutathione as a redox mediator to promote sustained generation and localized retention of electrochemical products (Zn2+ and Mn2+). These elements trigger the ICD effect through reactive oxygen species accumulation and stimulate the STING pathway to activate immune cells effectively. Strategic placement of this battery around subcutaneous tumor sites results in a 99.6% growth inhibition rate after a 14-day treatment. This work demonstrates a powerful electrochemical tool for drug-free cancer immunotherapy, which may open an avenue for sustained and localized delivery of immune agonists.
研究领域:
肿瘤学
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生物医学工程
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免疫学
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Zhicheng Zhang,Xiaoyan Sun,Yaxin Qin,Yufan Yang,Qi Dai,Xiaoyan Bao,Minoru Suzuki,Sheng Wang,Zai Yang,Zhifeng Li,Min Han,Donghang Xu,Qichun Wei
Boron Neutron Capture Therapy (BNCT) offers selective tumor cell ablation with minimal damage to normal tissues, but its efficacy is limited by therapy-induced immunosuppression and high intratumoral H 2 O 2 levels, restricting synergy with immunotherapy. Here, we report BSA-BPA-MnO 2 , a tumor microenvironment-responsive, manganese-enriched nanoboron agent designed to overcome these barriers. This nanoplatform combines efficient boron delivery with Mn 2+ -driven Fenton-like catalysis and cGAS-STING pathway activation, amplifying BNCT-induced oxidative stress and inducing immunogenic pyroptosis alongside robust type I interferon signaling. This dual mechanism transforms BNCT from a local therapy into a systemic immune activator, enhancing dendritic cell maturation and CD8 + T cell responses. Additionally, MnO₂ enables MRI-guided BNCT, integrating diagnostics and therapeutics. Notably, the platform achieves potent tumor suppression and systemic immune activation even at subclinical boron levels, offering a promising strategy for next-generation immune-integrated BNCT, particularly against melanoma.
研究领域:
癌症免疫治疗
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纳米医学
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放射肿瘤学
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分子影像学
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免疫代谢
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生物医学工程
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Advanced Healthcare Materials
·
2026
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IF 11
Jiajia Jia,Zhitong Guan,Jiaxin Wang,Ting Fang,Jiajun Sun,Aiyang Tong,Yingzhen Fan,Ming Zhao,Dongkai Wang,Zheran Wang,Ji Li
Although cGAS-STING immunotherapy holds immense potential, its efficacy is severely compromised by pathway evasion. To overcome this, we engineered a core-shell bilayer nanobomb (M/ZIF/MnO 2 @DBCO) via a template-assisted approach, integrating MSC1094308 into ZIF-8 cores followed by MnO 2 shell deposition and DBCO functionalization. In a simulated tumor microenvironment, ZIF-8 loading accelerated Mn 2+ release from MnO 2 , increasing the cumulative release by nearly 30% within 8 h compared to pristine MnO 2 . Cellular assays demonstrated rapid bio-orthogonal targeting of azide-modified tumors, achieving lysosomal escape within 6 h postuptake. Subsequently, MnO 2 -mediated glutathione (GSH) depletion and hydroxyl radical (·OH) generation, combined with Zn 2+ induced mitochondrial oxidative stress, produced cytotoxic reactive oxygen species (ROS) that triggered immunogenic cell death. Furthermore, Mn 2+ , Zn 2+ , and dsDNA released from damaged mitochondria cooperatively activated the cGAS-STING pathway. Concurrently, MSC1094308 inhibited ESCRT-mediated negative regulation, as evidenced by a ∼0.2 decrease in the p-STING/VPS4B-RFP colocalization coefficient, confirming the blockade of cGAS-STING evasion. In vivo studies revealed that the nanoplatform profoundly stimulated antitumor immunity, increasing tumor-infiltrating cytotoxic T lymphocytes approximately 8-fold versus untreated controls after 21 days. This work establishes an integrated strategy harnessing Zn 2+ /Mn 2+ synergy, nanobomb reactivity, and ESCRT inhibition to circumvent cGAS-STING evasion, offering a promising paradigm for cancer immunotherapy.
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