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

Fangming Zhang,

Ziyao Zhang, Wanting Yang

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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

Language: Английский

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

Xueyan Zhen

et al.

Med, Journal Year: 2025, Volume and Issue: 6(1), P. 100562 - 100562

Published: Jan. 1, 2025

Language: Английский

Citations

6
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment DOI Creative Commons
Jing Wei, Wenke Li, Pengfei Zhang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 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

Language: Английский

Citations

10
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

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 300, P. 140223 - 140223

Published: Jan. 22, 2025

Language: Английский

Citations

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

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 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

Language: Английский

Citations

8
ATP-responsive tumor targeted lipid nanoparticle for enhanced siRNA delivery and improved treatment efficacy in melanoma DOI
Lin Xiong, Shuang Chen, Sihui Li

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113622 - 113622

Published: March 1, 2025

Language: Английский

Citations

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

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 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.

Language: Английский

Citations

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

Lanfang Guo

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 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.

Language: Английский

Citations

0
A Multimodal Framework to Uncover Drug-Responsive Subpopulations in Triple-Negative Breast Cancer DOI Open Access
Yue Wang, Santiago Haase, Austin A. Whitman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

0
Epigenetic mechanisms in melanoma development and progression DOI
Hyunjeong Joo,

Ximena Diaz Olea,

Aojia Zhuang

et al.

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

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

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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

Language: Английский

Citations

0