Precisely Targeting TGF‐β1 Promoter G‐Quadruplex for Expediting Maturation of Tumor Dendritic Cells to Overcome Immune Evasion DOI
Chenglong Ma, Yue Sun,

Huaibing Yuan

et al.

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: May 29, 2025

Abstract The maturation of dendritic cells (DCs) represents a pivotal determinant in tumor immunotherapy efficacy. In advanced tumors, the immune‐suppressive transforming growth factor‐beta 1 (TGF‐β1) is frequently overexpressed and plays central role immune suppression. Elevated TGF‐β1 levels significantly impair DCs maturation, leading to reduced expression major histocompatibility complex (MHC) molecules inflammatory cytokines, consequently diminishing DCs‐mediated T cell activation. Here, this work first validates presence stable G‐quadruplex (G4) structure within promoter region. To minimize off‐target effects, establishes system precisely targeting G4. Through CRISPR‐mediated precise G4 by ligand biotin‐labeled pyridodicarboxamide (Bio‐PDC), demonstrates its functional downregulating expression. By combing ZIF‐8 as carrier Bio‐PDC, downregulation enhanced dual pathway, which subsequently facilitated maturation. These results highlight key regulatory suggest therapeutic potential synergistic target for enhancing efficacy counteracting evasion mechanisms.

Language: Английский

Platinum nanoparticles in cancer therapy: chemotherapeutic enhancement and ROS generation DOI

Emmanuel Faderin,

Terungwa H. Iorkula, Omowunmi Rebecca Aworinde

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 9, 2025

Language: Английский

Citations

4
Self-assembling chemodrug fiber-hydrogel for transarterial chemoembolization and radiotherapy-enhanced antitumor immunity DOI
Yisheng Peng, Hui Liu,

Xiaoliu Liang

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 1 - 16

Published: Feb. 3, 2025

Language: Английский

Citations

3
Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy DOI Creative Commons
Zaigang Zhou,

Wenjuan Luo,

Chunjuan Zheng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(9), P. 4087 - 4101

Published: June 3, 2024

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to impaired PTX@Alb accumulation in tumors partly mediated by dense collagen distribution. Meanwhile, acquired immune resistance always occurs enhanced programmed cell death-ligand 1 (PD-L1) expression after treatment, which then leads tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be as novel effective PD-L1 and TGF-

Language: Английский

Citations

12
A mitochondria-interfering nanocomplex cooperates with photodynamic therapy to boost antitumor immunity DOI
Zhijie Zhang,

Qingfu Zhao,

Qingqing Xu

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123094 - 123094

Published: Jan. 7, 2025

Language: Английский

Citations

2
The Role of cGAS-STING in Remodeling the Tumor Immune Microenvironment Induced by Radiotherapy DOI
Qingyu Jiang,

Zhiheng Chen,

Jin Jiang

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 209, P. 104658 - 104658

Published: Feb. 15, 2025

Language: Английский

Citations

2
Enzymatically responsive nanocarriers targeting PD-1 and TGF-β pathways reverse immunotherapeutic resistance and elicit robust therapeutic efficacy DOI Creative Commons
Ying‐Tzu Yen, Zhifan Zhang, Anni Chen

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 19, 2025

Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment, yet resistance remains a challenge. Co-inhibition of PD-1/PD-L1 and TGF-β shows promise but faces limited efficacy systemic toxicity. We developed gelatinase-responsive nanoparticles (GPNPs) delivering anti-PD-1 antibody (αPD-1) receptor I inhibitor galunisertib (Gal). GPNPs effectively inhibit tumor progression without observed side effects. profiling by cytometry assay reveals robust recruitment both activated exhausted tumor-infiltrating lymphocytes (TILs) macrophages. Transcriptomic analysis indicates extracellular matrix modulation, supported reduced collagen deposition αSMA expression. Fate mapping demonstrates attenuation Pdgfrα+ fibroblast transition to myofibroblasts, potentially reversing "immune-exclusive" status. This study validates as promising immunotherapy platform, offering mechanistic insights for clinical translation therapeutic enhancement.

Language: Английский

Citations

2
Is an immune-oriented use of radiation therapy possible? An increasingly open question under the spotlight of immunotherapy DOI Creative Commons

Valentina Zagardo,

Mandara Harikar, Gianluca Ferini

et al.

ONCOLOGIE, Journal Year: 2024, Volume and Issue: 26(3), P. 487 - 491

Published: March 7, 2024

Abstract Historically, radiation therapy has been devoted to the achievement of local control both in early and advanced disease, palliation symptoms (i.e. pain), treatment cancer complications bone fractures, bleeding) advanced/metastatic cancer. Recently, discovery role as a trigger activate immune system led an increased interest among insiders regarding interaction between host reactions. The systemic effects are widely acknowledged be immunosuppressive immunostimulant, albeit there exists considerable uncertainty doses/fraction that can induce them. main aim this brief paper is describe anti-tumor responses following on basis selected doses/fraction.

Language: Английский

Citations

7
Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction DOI Creative Commons
Honglei Hu,

Shuting Zheng,

Chenxi He

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 9, 2024

Abstract Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO 2 ) that was core coated with MnO shell followed by glucose oxidase (GOx) doping nanoplatform @MnO @GOx, HMG) to trigger ferroptosis adjuvant effects glutathione depletion and reactive oxygen species production. This cascade potentiation further sensitized radiotherapy enhancing DNA damage in 4T1 breast tumor cells. The combination of HMG nanoparticles effectively activated the damaged Mn 2+ -mediated cGAS-STING pathway vitro vivo. process had significant inhibitory on progression initiating an anticancer systemic response prevent distant recurrence achieve long-lasting suppression both primary tumors. Furthermore, as-prepared “turned on” spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, demonstrated favorable contrast enhancement capabilities under GSH microenvironment. result highlighted potential as theranostic achieving molecular guided sensitization induced synergistic immunotherapy.

Language: Английский

Citations

7
Activating the cGAS-STING Pathway by Manganese-Based Nanoparticles Combined with Platinum-Based Nanoparticles for Enhanced Ovarian Cancer Immunotherapy DOI

Xiangling Zhang,

Dongsheng Tang, Haihua Xiao

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Recent research has demonstrated that activating the cGAS-STING pathway can enhance interferon production and activation of T cells. A manganese complex, called TPA-Mn, was developed in this context. The reactive oxygen species (ROS)-sensitive nanoparticles (NPMn) loaded with TPA-Mn are developed. NPMn activates via cGAS (i.e., 1.6-fold enhancement P-STING), which turn increases secretion pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-2). This promotes dendritic cell maturation, enhances infiltration cytotoxic lymphocytes, reduces percentage immunosuppressive regulatory In addition, it is crucial to emphasize cisplatin-induced DNA damage potentially trigger pathway. NPMn, combination low-dose NPPt, a carrier Cis(IV) prodrug capable causing damage, augments significantly tumor immune microenvironment (TIME). Furthermore, combined anti-PD-1 antibody, NPPt+NPMn shows synergistic efficacy both ovarian cancer peritoneal metastases recurrence models. It not only effectively eliminates tumors but also induces strong memory response, providing promising strategy for clinical management cancer. work offers design manganese-based immunotherapy.

Language: Английский

Citations

1
Transformable Tumor Microenvironment‐Responsive Oxygen Vacancy‐Rich MnO2@Hydroxyapatite Nanospheres for Highly Efficient Cancer Sonodynamic Immunotherapy DOI Creative Commons

Minxing Li,

Qiyu Liu, Songzuo Xie

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Despite the promise of sonodynamic therapy (SDT)-mediated immunotherapy, anticancer efficacy current sonosensitizers is greatly limited by immunosuppressive tumor microenvironment (TME) and their inability to selectively respond it. Herein, oxygen vacancy-rich MnO2@hydroxyapatite (Ca10(PO4)6(OH)2) core-shell nanospheres (denoted as Ov-MO@CPO) an advanced TME-responsive sonosensitizer for immunotherapy demonstrated. The Ov-MO@CPO maintains its structural integrity under neutral conditions but dissolves pH-sensitive hydroxyapatite shell acidic TME release active MnO2 core, which reinvigorates H2O2 consumption hypoxia alleviation due catalase-like activity. Furthermore, introduced vacancies optimize electronic structure Ov-MO@CPO, with states near Fermi level higher d-band center. It results in accelerated electron-hole pair separation lower catalytic energy barriers boost ultrasound (US)-initiated ROS production. These multimodal synergistic effects effectively reverse microenvironment, inhibiting growth metastasis 4T1 tumor-bearing mice. No evident toxic are observed normal mouse tissues. Additionally, when combined immune checkpoint inhibitor, Ov-MO@CPO-mediated SDT further improves effectiveness immunotherapy. This work affords a new avenue developing TME-dependent SDT-mediated

Language: Английский

Citations

1