Engineering Autologous Cell‐Derived Exosomes to Boost Melanoma‐Targeted Radio‐Immunotherapy by Cascade cGAS‐STING Pathway Activation DOI

Fangming Zhang,

Ziyao Zhang, Wanting Yang

и другие.

Small, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

Abstract Radio‐immunotherapy has offered emerging opportunities to treat invasive melanoma due its immunostimulatory performances activate antitumor immune responses. However, the immunosuppressive microenvironment and insufficient response rate significantly limit practical efficacy. This study presents an autologous cell‐derived exosomes (Exo)‐engineered nanoagonist (MnExo@cGAMP) containing with metalloimmunotherapeutic agent (Mn 2+ ions) nucleotidyltransferase (2′,3′‐cGAMP, a STING agonist) for boosting melanoma‐targeted radio‐immunotherapy by cascade cGAS‐STING pathway activation. The MnExo@cGAMP can efficiently accumulate in tumor cells targeting performance. Once internalized cells, released Mn ions will enhance stimulator of interferon gene (STING) binding sensitize cyclic GMP‐AMP (cGAS) radiotherapy‐induced double‐straned DNA (dsNDA), resulting amplification activation together X‐ray irradiation. Meanwhile, loaded 2′,3′‐cGAMP directly augment activity acting as secondary messenger. These activations trigger overexpression type I interferon, promote dendritic (DCs) maturation, antigen presentation, increase CD8 + T cell activation, effective radio‐immunotherapeutic outcome overcoming immune‐suppression melanoma. demonstrates targeted therapeutic modality involving metalloimmunotherapy agonist efficient

Язык: Английский

Clinical advances of mRNA vaccines for cancer immunotherapy DOI Creative Commons
Alexey V. Yaremenko, Muhammad Muzamil Khan,

Xueyan Zhen

и другие.

Med, Год журнала: 2025, Номер 6(1), С. 100562 - 100562

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

4
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment DOI Creative Commons
Jing Wei, Wenke Li, Pengfei Zhang

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Дек. 26, 2024

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune blockade (ICB) remains critical challenge, characterized by variable response rates and non-durable benefits. However, growing research into complex intrinsic extrinsic characteristics tumors has advanced our understanding mechanisms behind ICI resistance, potentially improving outcomes. Additionally, robust predictive biomarkers are crucial optimizing patient selection maximizing efficacy ICBs. Recent studies emphasized that multiple rational combination strategies can overcome enhance susceptibility ICIs. These findings not only deepen tumor biology but also reveal unique action sensitizing agents, extending benefits in cancer immunotherapy. In this review, we will explore underlying ICIs, discuss significance microenvironment (TIME) biomarkers, analyze current outline alternative effectiveness including personalized

Язык: Английский

Процитировано

8
Chondroitin sulfate-based dissolvable microneedles loaded with NIR-II photothermal and natural anticancer agents for synergistic melanoma therapy DOI
Yushan Li, Zhaoyi Ye,

Huiling Ye

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 300, С. 140223 - 140223

Опубликована: Янв. 22, 2025

Язык: Английский

Процитировано

1
Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications DOI Creative Commons
Zhengjun Lin, Guoqing Li, Ke Jiang

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Сен. 7, 2024

Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs critically involved shaping structure function microenvironment with numerous functions regulating behaviours, such as metastasis, invasion, epithelial-mesenchymal transition (EMT). can interact extensively cells by producing extracellular vesicles (EVs), multiple secreted factors, metabolites. Notably, CAF-derived EVs been critical mediators therapy resistance, constitute novel targets biomarkers management. This review aimed to summarize biological detailed molecular mechanisms mediating resistance chemotherapy, targeted agents, radiotherapy, immunotherapy. We also discussed therapeutic potential clinical management, thereby providing strategy for enhancing efficacy improving

Язык: Английский

Процитировано

8
A Multimodal Framework to Uncover Drug-Responsive Subpopulations in Triple-Negative Breast Cancer DOI Open Access
Yue Wang, Santiago Haase, Austin A. Whitman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Abstract Understanding how individual cancer cells adapt to drug treatment is a fundamental challenge limiting precision medicine therapy strategies. While single-cell technologies have advanced our understanding of cellular heterogeneity, efforts connect the behavior broader tumor responses and uncover global trends across diverse systems remain limited. There growing availability bulk omics data, but lack centralized tools repositories makes it difficult study response globally, especially at level adaptation. To address this, we present multimodal framework that integrates treated untreated transcriptomics data identify responsive cell populations in triple-negative breast (TNBC). Our leverages population-scale from TNBC samples define seven main “identities”, each representing unique combinations biologically relevant genes. These identities are dynamic trackable, allowing us map them onto single patterns respond treatment. Unlike static classifications, this approach captures evolving nature states, revealing select few dominate drive population-level during Crucially, ability decode these through inherent noise provides clearer picture heterogeneous therapy. By identifying dominant their dynamics, can better predict entire tumors This insight essential for designing precise combination therapies tailored heterogeneity patient tumors, addressing variations ultimately determine therapeutic outcomes.

Язык: Английский

Процитировано

0
ATP-responsive tumor targeted lipid nanoparticle for enhanced siRNA delivery and improved treatment efficacy in melanoma DOI
Lin Xiong, Shuang Chen, Sihui Li

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113622 - 113622

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Mechanistic insights into proteasome inhibitor MG132 induced apoptosis in melanoma A375 cells DOI Creative Commons
Meng Xu, Ziqing Zhang, Xinyi He

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 27, 2025

Despite advancements in melanoma therapy, the prognosis remains unfavorable for many patients. The proteasome inhibitor MG132 has shown therapeutic potential through pathway regulation, yet its precise mechanisms require systematic elucidation. Using A375 cells, we conducted multi-modal investigations combining cytotoxicity assessment (CCK8), migration analysis (wound healing), apoptosis quantification (flow cytometry), and proteomic profiling (western blot) to dissect MG132's molecular mechanisms. Our findings revealed potent anti-tumor activity with an IC50 of 1.258 ± 0.06 µM, significantly suppressing cellular at concentrations. Apoptosis assays demonstrated concentration-dependent effects, 2 µM treatment inducing early 46.5% total apoptotic response 85.5% cells within 24 h. Mechanistic studies uncovered dual regulatory capacity: (1) Through MDM2 inhibition, it activated p53/p21/caspase-3 axis while CDK2/Bcl2, triggering cell cycle arrest DNA damage cascades; (2) MAPK activation emerged as a critical driver. Notably, western blot established dose-responsive modulation these targets, confirming specificity. results position multi-target agent capable simultaneously disrupting proliferative signaling activating machinery. observed MAPK-mediated mechanism provides novel insights therapeutics, suggesting that combinatorial targeting proteasomal pathways may enhance efficacy.

Язык: Английский

Процитировано

0
The molecular mechanisms, roles, and potential applications of PANoptosis in cancer treatment DOI Creative Commons
Wenyuan Ma, Qiang Wang,

Lanfang Guo

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 29, 2025

PANoptosis, a newly identified form of programmed cell death regulated by the panoptosome complex, exhibits key characteristics apoptosis, pyroptosis and necroptosis. It exerts substantial influence on initiation progression spectrum diseases, particularly in cancer, where its impact is increasingly being recognized. PANoptosis closely related to tumorigenesis, carcinogenesis, metastasis, chemotherapy resistance, as well prediction therapeutic responses prognosis cancer patients. In this review, we first review discovery systematically analyze composition panoptosome. Subsequently, examine role various types encompassing function within tumor microenvironment, drug predictive prognosis. Ultimately, delve into strategies for targeting therapy, including molecules pathway, such ZBP1, RIPK1, RIPK3, Caspases other novel like nanoinducers viral vectors. This aims provide references assistance research application treatment.

Язык: Английский

Процитировано

0
Engineering Autologous Cell‐Derived Exosomes to Boost Melanoma‐Targeted Radio‐Immunotherapy by Cascade cGAS‐STING Pathway Activation DOI

Fangming Zhang,

Ziyao Zhang, Wanting Yang

и другие.

Small, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

Abstract Radio‐immunotherapy has offered emerging opportunities to treat invasive melanoma due its immunostimulatory performances activate antitumor immune responses. However, the immunosuppressive microenvironment and insufficient response rate significantly limit practical efficacy. This study presents an autologous cell‐derived exosomes (Exo)‐engineered nanoagonist (MnExo@cGAMP) containing with metalloimmunotherapeutic agent (Mn 2+ ions) nucleotidyltransferase (2′,3′‐cGAMP, a STING agonist) for boosting melanoma‐targeted radio‐immunotherapy by cascade cGAS‐STING pathway activation. The MnExo@cGAMP can efficiently accumulate in tumor cells targeting performance. Once internalized cells, released Mn ions will enhance stimulator of interferon gene (STING) binding sensitize cyclic GMP‐AMP (cGAS) radiotherapy‐induced double‐straned DNA (dsNDA), resulting amplification activation together X‐ray irradiation. Meanwhile, loaded 2′,3′‐cGAMP directly augment activity acting as secondary messenger. These activations trigger overexpression type I interferon, promote dendritic (DCs) maturation, antigen presentation, increase CD8 + T cell activation, effective radio‐immunotherapeutic outcome overcoming immune‐suppression melanoma. demonstrates targeted therapeutic modality involving metalloimmunotherapy agonist efficient

Язык: Английский

Процитировано

0