International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Shiying Xu,Lina Wu,Boxin Chen,Xiaoliang Deng,Zhihui Zheng,Fei Wu,Lingjun Zeng,Changqing Zheng,Xiaomu Hu,Aiwen Huang,Xin Zhou,Xianquan Feng,Zhihong Liu
Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment due to its selective tumor ablation and excellent safety characteristics. However, its efficacy is limited by tumor hypoxia and excessive inflammation. In this study, we fabricated human serum albumin-based nanoparticles (CAI NPs) encapsulating celecoxib (CXB), atovaquone (ATO), and IR820 via sonication. The CAI NPs exhibited favorable physicochemical properties, including a uniform size distribution (<200 nm), high encapsulation efficiency and excellent colloidal stability. Initially, ATO acts as a mitochondrial complex III inhibitor, suppressing oxidative phosphorylation to ameliorate tumor hypoxia. This hypoxia alleviation potentiates PDT efficacy by enhancing tumor cell ROS generation. Furthermore, concomitant COX-2/PGE2 inhibition by CXB attenuates the excessive inflammatory cascade triggered during PDT, resulting in enhanced therapeutic outcomes through microenvironment modulation. Eventually, the dual-enhanced CAI NPs demonstrate potent antitumor activity in both in vivo and ex vivo models, while maintaining excellent biocompatibility under physiological conditions. In summary, the integrated three-drug regimen conclusively enhances photodynamic therapeutic outcomes through multimodal mechanisms, establishing a viable treatment approach for esophageal cancer.
研究领域:
肿瘤学
·
纳米医学
·
光动力治疗
·
分子药理学
·
肿瘤微环境
·
转化医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 11
·311
·
IF 3.1
Qing Zhu,Yuanshan Han,Ying He,Yilan Fu,Hui Yang,Yun Chen,Yingrui Shi
Background: Breast cancer-related depression (BCRD) is strongly associated with BC and increases recurrence and mortality. This study investigated the role of kaempferol in the pathogenesis of BCRD and its underlying mechanism. Methods: 4T1 mouse BC cells were treated with corticosterone (Cort) in vitro to develop a neuronal injury model, and a BCRD mouse model was established by injecting 4T1 cells and Cort. The effects of kaempferol on 4T1 cells and BCRD models were measured by behavioral tests, Cell Counting Kit-8 assay, wound healing assay, colony formation assay, Western blot analysis, quantitative real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay, and immunofluorescence. BCRD cells were transfected with the cyclo-oxygenase-2 (COX-2) overexpression plasmid to study the role of the COX-2/prostaglandin E2 (PGE2) axis in the anti-BCRD activity of kaempferol. The connection between kaempferol and COX-2 was analyzed by molecular docking. Results: Kaempferol reduced the viability, migration, and clones of 4T1 cells and inhibited BC growth and depression-like behavior in mice. Kaempferol alleviated inflammation in BCRD, decreased interleukin 1 beta (IL-1β) and IL-6 levels, and increased transforming growth factor beta 1 (TGF-β1) and IL-10 levels. In addition, kaempferol elevated the levels of serotonin, dopamine, and norepinephrine and the amount of 5-Bromo-2′-deoxyuridine/neuronal nuclei-positive cells. Kaempferol downregulated COX-2 and PGE2, and kaempferol could dock with the protein structure of COX-2. Overexpression of COX-2 reduced BCRD viability, upregulated IL-1β and IL-6 levels, and downregulated TGF-β1 and IL-10 expression. Overexpression of COX-2 reversed the protective effects of kaempferol. Conclusion: Kaempferol exerted anti-BCRD effects, at least in part by inhibiting the COX-2/PGE2 pathway, which regulates neuroinflammation, neurotransmitter imbalance, and defective neurogenesis. Therefore, kaempferol may be a promising candidate active ingredient for treating BCRD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Zhang Yiling,Li Yu,Lu Jiayu,Qin Xin,Wang Zixin,Cai Aojie,Fan Ling,Jin Ronghua,Xie Yandong
To address the therapeutic limitations and metabolic toxicity associated with conventional nanocarriers, a nanostructure using an “MOF-in-MOF” strategy was engineered. The comprises an olsalazine (Olsa)-based copper metal-organic framework (Olsa-MOF) that integrates intrinsic anti-inflammatory properties and enhanced chemodynamic performance. This Olsa-MOF template is integrally enveloped by a tumor microenvironment-responsive TK-based Cu-MOF layer, which demonstrates exceptional photothermal properties. Subsequent surface functionalization with dopamine-grafted hyaluronic acid (DOPA-HA) endows active targeting ability, yielding the final nanocomposite termed Olsa@TK-Cu@HA. Olsa@TK-Cu@HA not only overcomes the limitations of conventional nanocarriers but also offers a novel strategy to enhance the therapeutic efficacy of photothermal therapy (PTT) and chemodynamic therapy (CDT) through targeted modulation of the COX-2/PGE2 inflammatory axis. The Olsa@TK-Cu@HA demonstrates a superior photothermal conversion efficiency (26.8%) and robust reactive oxygen species (ROS) generation, along with pH-responsive release of Olsa. In vitro evaluation demonstrated that Olsa@TK-Cu@HA exerts tumor-selective cytotoxicity, showing 3.5-fold higher potency against cancer cell. Moreover, Olsa@TK-Cu@HA effectively induces immunogenic cell death (ICD), as evidenced by increased extracellular ATP efflux (5.06-fold elevation) and CRT exposure. Concurrently, it downregulates the COX‑2/PGE2 axis to relieve immunosuppression in the tumor microenvironment and suppresses PD‑L1 expression. This coordinated action amplifies ICD‑mediated antitumor immunity, leading to a tumor regression rate of 84.0% in vivo. By integrating precision targeting, stimulus-responsive drug release, and immunometabolic reprogramming, this work moves beyond conventional treatment paradigms and establishes an innovative platform for next‑generation cancer therapy. Graphical The alternative text for this image may have been generated using AI.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 13.6
Dandan Mi,Tiantian Liu,Lan Zou,Yuyu Wei,Jun Zeng,Chunxiao Nie,Yi Zeng,Rujing Wang,Mengnan Zhao,Sanjun Shi
Surgical resection combined with chemotherapy remains the standard clinical intervention for triple-negative breast cancer (TNBC). However, the elevated expression of COX-2/PGE 2 , often exacerbated by chemotherapeutic agents, is significantly associated with high postoperative recurrence and metastasis. Tailored for the TNBC postoperative setting, we developed a photopolymerizable, dual-asymmetric hemostatic Janus hydrogel patch (DJ-Patch) based on the synergistic pharmacodynamic rationale of gambogic acid (GA) and celecoxib (CXB) pairing. The DJ-Patch exhibits a stratified bilayer configuration comprising a rapid-release layer (5% GelMA) encapsulating GA, juxtaposed with an extended-release layer (10% GelMA/2.5% PEGNB) containing the selective COX-2 inhibitor CXB. In vitro study corroborated this differential release modality, revealing asymmetric kinetics wherein GA achieved ∼20% release at 8 h escalating to greater than 60% by day 3, whereas CXB demonstrated ∼10% release at 8 h and ∼30% by day 3. In vivo release profiles further substantiated these findings, demonstrating that CXB exhibited a 2-fold prolonged release duration relative to GA. The asymmetric adhesive design, featuring a high-adhesion interface manifesting adhesion strength 12.5-fold superior to GelMA alone, facilitated rapid intraoperative hemostasis with clotting time reduced to 160 s versus 440 s in untreated controls, and effected efficacious wound sealing as validated in a mouse liver laceration model. In an orthotopic 4T1-Luc TNBC resection model, the DJ-Patch achieved 86% survival, complete tumor clearance by day 7, and suppressed lung metastasis through sustained COX-2/PGE 2 axis inhibition, Treg cell reduction, and remodeled the immunosuppressive tumor microenvironment (TME). Collectively, this integrated platform offers a promising strategy for comprehensive TNBC postsurgical management.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2025
·Vol. 44
·期 1
·321
·
IF 12.8
Lei Yu,Bai Yaowei,Bai Xiatong,Sun Bo,Zhu Licheng,Wu Wenlong,Su Yang,Zhang Hongsen,Wang Yingliang,Zheng Chuansheng
Background and aims Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but incomplete ablation and recurrence of residual tumors remain significant challenges, partly due to local inflammation and elevated COX-2 levels in the tumor microenvironment. This study aims to investigate the potential of combining celecoxib, a COX-2 inhibitor, with anti-PD-1 monoclonal antibody (αPD-1) to enhance anti-tumor efficacy and activate immune responses. Methods In vitro, ELISA was used to assess the effects of radiofrequency heat treatment and celecoxib on PGE 2 secretion by Hepa1-6 cells. Scanning electron microscopy, flow cytometry, and CCK-8 assays were employed to evaluate the function and cytotoxic activity of NK92 cells against Hepa1-6 cells. In vivo, orthotopic HCC mice were divided into five groups to evaluate tumor volume, pathology, and survival. The role of celecoxib in the COX-2/PGE 2 /NK cell axis and its impact on NK cell immune function were investigated. Results In vitro experiments showed that celecoxib reversed PGE 2 -mediated suppression of NK cell function and cytotoxic activity against HCC cells by inhibiting PGE 2 secretion. In vivo, orthotopic HCC mice treated with celecoxib and αPD-1 exhibited significantly reduced tumor volumes, attenuated the infiltration and activation of NK cells, and prolonged survival compared to control groups. The combination therapy also demonstrated a notable abscopal-like effect, inhibiting metastatic tumor growth and activating systemic immunity. Conclusions Taken together, these findings suggest that celecoxib combined with αPD-1 represents a promising strategy for treating residual HCC after RFA, with enhanced anti-tumor effects and good safety. Graphical abstract
研究领域:
肿瘤学
·
免疫治疗
·
分子生物学
·
癌症免疫学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 8
·177
·
IF 3.1
Pingping Lv,Huirong Zhang,Meiling Tai,Biao Che,Dan Yu,Ying Zhang,Haodong Li,Xianyao Meng,Miaomiao Guo,Li Li
Background: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. Methods: In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO’s anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry. Results: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. Conclusions: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.
研究领域:
药理学
·
皮肤科
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Chenqi Guo,Mengying Wu,Zhaofei Guo,Rongping Zhang,Zijun Wang,Xiong Peng,Jianxia Dong,Xun Sun,Zhirong Zhang,Peihong Xiao,Tao Gong
Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified and secreted by swollen Golgi apparatus in tumor cells. Thus, Golgi complex is considered as an important target for the remedy of metastasis. Currently, Golgi targeting technologies are mostly employed in Golgi-specific fluorescent probes for diagnosis, but their applications in therapy are rarely reported. Herein, we proposed a prodrug (INR) that can target and destroy the Golgi apparatus, which consisted of indomethacin (IMC) as the Golgi targeting moiety and retinoic acid (RA), a Golgi disrupting agent. The linker between IMC and RA was designed as a hypoxia-responsive nitroaromatic structure, which ensured the release of the prototype drugs in the hypoxic tumor microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), an anthracycline, to form a carrier-free nanoparticle (NP) by emulsion-solvent evaporation method. A small amount of mPEG2000-DSPE was added to shield the positive charges and improve the stability of the nanoparticle to obtain PEG-modified nanoparticle (PNP). It was proved that INR released the prototype drugs in tumor cells and hypoxia promoted the release. The Golgi destructive effect of RA in INR was amplified owing to the Golgi targeting ability of IMC, and IMC also inhibited the protumor COX-2/PGE2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary tumor and its pulmonary and hepatic metastasis. The small molecular therapeutic prodrug targeting Golgi apparatus could be adapted to multifarious drug delivery systems and disease models, which expanded the application of Golgi targeting tactics in disease treatment.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Xianquan Feng,Yan Zhang,Wanjing Lin,Jing Li,Fei Wu,Qingyu Lu,Hongtao Song,Hao Zhang,Fenghua Lan,Jun Lu
The efficacy of immunotherapy in triple-negative breast cancer (TNBC) is significantly hindered by its low immunogenicity and immunosuppressive tumor microenvironment. Non-invasive photodynamic therapy (PDT) is increasingly recognized as a potential immunotherapeutic stimulant in the treatment of TNBC. However, photodynamic immunotherapy is constrained by tumor hypoxia and excessive inflammation suppression during the course of treatment. Herein, a simple and efficacious biomedicine is formulated to overcome adverse influences by amplifying photodynamic immunotherapy, thereby stimulating the systemic immune response. Specifically, the approach targeted tumor delivery by employing specific agents such as the photosensitizer (verteporfin), the hypoxic ameliorator (atovaquone), and the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) signaling blocker (celecoxib). More importantly, the biomedicine effectively ameliorated hypoxia and inhibited COX-2/PGE2 signaling, thereby amplifying PDT-induced immunogenic cell death. This, in turn, enhanced the efficacy of photodynamic immunotherapy and triggered a robust immune response cascade. Notably, the self-amplifying photodynamic biomedicine significantly inhibited primary tumors, distal tumors, lung metastases, and post-operative recurrence while maintaining high biocompatibility. To sum up, the work provides a viable cascade stimulation approach and an efficient biomedical nanoplatform, offering a novel strategy for photodynamic immunotherapy of TNBC in the clinic.
研究领域:
肿瘤学
·
免疫学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xiaoliang Deng,Xianquan Feng,Xiaohui Tang,Zhihui Zheng,Da Zheng,Enqin Zheng,Lingjun Zeng,Shiying Xu,Boxin Chen,Qian Zhang,Zhihong Liu,Hongtao Song
The clinical efficacy of immunotherapy in triple-negative breast cancer (TNBC) faces dual barriers: poor immunogenicity and a suppressive tumor microenvironment. While low-temperature photothermal therapy (LTPTT) has emerged as a potential immunostimulatory strategy, its efficacy is counteracted by heat shock protein (HSP) induction and COX-2/PGE2-mediated immunosuppression. To address these challenges, we developed a multifunctional immunophotothermal nanoplatform (IAC NPs) through rational engineering of human serum albumin for combinatorial delivery of indocyanine green as a photothermal converter, atovaquone for HSP70-mediated thermoresistance blockade, and celecoxib for COX-2/PGE2 pathway inhibition. The IAC NPs achieved tumor-targeted delivery and NIR-activated immunogenic phototherapy while coinhibiting HSP70 (via atovaquone’s mitochondrial complex III blockade) and the COX-2/PGE2 immunosuppressive axis (via celecoxib). The triple medications’ synergistic action improved the expression of effector memory T cells, boosted the maturation of dendritic cells, encouraged the infiltration of CD4+ and CD8+ T cells, and reduced regulatory T cells. In vivo, the IAC NPs mediated profound suppression of both primary tumors and metastatic dissemination while exhibiting optimal biocompatibility for clinical translation. Our work validates a nanoenabled self-delivery system that augments the efficacy of LTPTT immunotherapy against TNBC by orchestrating coordinated inhibition of HSPs and inflammatory responses.
研究领域:
癌症免疫治疗
·
纳米医学
·
光热治疗
·
分子靶向治疗
·
肿瘤微环境
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）