Mitochondria- and Anaerobic Glycolysis- Targeted Self-Assembled Copper Complex Nanoparticles for Boosting Cuproptosis- Immunotherapy DOI Creative Commons
Hanyu Zhang,

Jing Xia,

Lingling Xie

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Abstract Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing specific accumulation of ions mitochondria while simultaneously enhancing respiration are highly needed still a major challenge to promote cuproptosis. Herein, lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with ionophore elesclomol (ES) through ion-driven cooperative coordination form GF/CuES nanoparticles, synergistically targeting anaerobic glycolysis boost cuproptosis-immunotherapy. After cellular internalization, nanoparticles responsively dissociate release Cu2+ ES, co-transporting into collaboratively trigger cuproptosis, which subsequently evokes immunogenic (ICD). Notably, liberated GF leads effective LDH suppression, not only further amplifies cuproptosis via disrupting but also reduces production, thus alleviating immunosuppressive tumor microenvironment augmenting anti-tumor immunity driven by ICD. Thus, exhibit strong antitumor effects cooperatively glycolysis, immunotherapy, offering unique opportunity enhance treatment strategies.

Language: Английский

Ginger-Derived Exosome-Like Nanoparticles Loaded With Indocyanine Green Enhances Phototherapy Efficacy for Breast Cancer DOI Creative Commons
Zhaoming Guo, Guqing Li,

Lanjun Shen

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 1147 - 1169

Published: Jan. 1, 2025

Phototherapy has remarkable advantages in cancer treatment, owing to its high efficiency and minimal invasiveness. Indocyanine green (ICG) plays an important role photo-mediated therapy. However, it several disadvantages such as poor stability aqueous solutions, easy aggregation of molecules, short plasma half-life. This study aimed develop efficient nanoplatform enhance the effects We developed a novel bio-nanoplatform by integrating edible ginger-derived exosome-like nanoparticles (GDNPs) photosensitizer, ICG (GDNPs@ICG). GDNPs were isolated from ginger juice loaded with co-incubation. The size distribution, zeta potential, morphology, total lipid content, drug release behavior GDNPs@ICG characterized. photothermal performance, cellular uptake cytotoxicity, anti-tumor effects, mechanism action investigated both vitro vivo. taken up tumor cells via lipid-dependent pathway. When irradiated 808 nm NIR laser, generated levels ROS, MDA, local hyperthermia within tumor, which caused peroxidation ER stress, thus enhancing breast therapy effect. Furthermore, vivo studies demonstrated that engineered significantly inhibited growth presented limited toxicity. Moreover, detecting expression CD31, N-cadherin, IL-6, IFN-γ, CD8, p16, p21, p53 tissues, we found substantially reduced angiogenesis, metastasis, activated immune response, promoted cell senescence tumor. Our enhanced therapeutic effect could be alternative for precise phototherapy.

Language: Английский

Citations

1
Exploring the role of the immune microenvironment in hepatocellular carcinoma: Implications for immunotherapy and drug resistance DOI Creative Commons
Yumin Fu, Xinyu Guo, Linmao Sun

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 15, 2024

Hepatocellular carcinoma (HCC), the most common type of liver tumor, is a leading cause cancer-related deaths, and incidence cancer still increasing worldwide. Curative hepatectomy or transplantation only indicated for small population patients with early-stage HCC. However, HCC are not candidates radical resection due to disease progression, choice conventional tyrosine kinase inhibitor drug sorafenib as first-line treatment. In past few years, immunotherapy, mainly immune checkpoint inhibitors (ICIs), has revolutionized clinical strategy Combination therapy ICIs proven more effective than sorafenib, trials have been conducted apply these therapies patients. Despite significant progress in molecular mechanisms behind it remain unclear, resistance often challenging overcome. Several studies pointed out that complex intercellular communication network microenvironment regulates tumor escape response. This underscores urgent need analyze review describes immunosuppressive cell populations HCC, well related trials, aiming provide insights next generation precision immunotherapy.

Language: Английский

Citations

5
Lactylation: The Metabolic Accomplice Shaping Cancer's Response to Radiotherapy and Immunotherapy DOI
Danqing Yu, Qingping Zhong, Yanlin Wang

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102670 - 102670

Published: Jan. 1, 2025

Language: Английский

Citations

0
Advances in Antibody-Based Immune-Stimulating Drugs: Driving Innovation in Cancer Therapy DOI Open Access

R R Zhao,

Xing-Xing Fan

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1440 - 1440

Published: Feb. 8, 2025

Antibody-based immune-stimulating drugs (ABIs) represent a transformative frontier in cancer immunotherapy, designed to reshape the tumor microenvironment and overcome immune suppression. This study highlighted recent advances ABIs, including antibody conjugates (ISACs), bispecific antibodies (BsAbs), checkpoint blockade enhancers, with focus on their mechanisms of action, clinical advancements, challenges. Preclinical findings revealed that ISACs effectively boost overall anti-cancer immunity by reprogramming tumor-associated macrophages, enhancing T cell activation, engaging other pathways. Similarly, BsAbs redirect cells tumors, achieving significant regression. Additionally, artificial intelligence (AI) is revolutionizing development ABIs optimizing drug design, identifying novel targets, accelerating preclinical validation, enabling personalized therapeutic strategies. Despite these challenges remain, resistance off-target effects. Future research should prioritize next-generation multifunctional antibodies, AI-driven innovations, combination therapies enhance efficacy expand applications. Connecting gaps could unlock full potential upgrading treatment improving outcomes for patients refractory or resistant tumors.

Language: Английский

Citations

0
Galloflavin mitigates acute kidney injury by suppressing LDHA-dependent macrophage glycolysis DOI Creative Commons

Jie Wei,

Xinyu Chen, Zhijuan Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114265 - 114265

Published: Feb. 16, 2025

Macrophage-mediated inflammation is closely linked to the pathogenesis of acute kidney injury (AKI) and shift macrophages a pro-inflammatory phenotype being reliant on glycolytic metabolism. Galloflavin, polyphenol derived from tea, functions as lactate dehydrogenase A (LDHA) inhibitor, effectively obstructing metabolic pathways. However, specific immunometabolic regulatory galloflavin in remain unclear. Here, we observed that drives alleviation metabolism levels lipopolysaccharide (LPS)-induced (RAW264.7 cells human peripheral blood mononuclear cells-derived macrophages) through downregulation LDHA expression, thereby inhibiting macrophage conversion reducing release inflammatory cytokines. overexpression counteracts effects macrophages. In addition, vivo experiments protective effect against cecal ligation puncture (CLP) cisplatin-induced renal injury. The ability inhibit glycolysis macrophages, regulating their phenotypic transition during AKI was further validated isolation primary This intervention ultimately ameliorated response decelerated progression AKI. Collectively, confers protection by suppressing LDHA-dependent mechanism, positioning it potential therapeutic option for future.

Language: Английский

Citations

0
Research progress on the regulatory role of lactate and lactylation in tumor microenvironment DOI
Chunyan Gao,

Jiali Li,

Baoen Shan

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189339 - 189339

Published: April 1, 2025

Language: Английский

Citations

0
Targeting Lactate: An Emerging Strategy for Macrophage Regulation in Chronic Inflammation and Cancer DOI Creative Commons

Rong Jiang,

Wenjing Ren,

Liying Wang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1202 - 1202

Published: Sept. 24, 2024

Lactate accumulation and macrophage infiltration are pivotal features of both chronic inflammation cancer. Lactate, once regarded merely as an aftereffect glucose metabolism, is now gaining recognition for its burgeoning spectrum biological roles immunomodulatory significance. Recent studies have evidenced that macrophages display divergent immunophenotypes in different diseases, which play a role disease management by modulating polarization within the microenvironment. The specific patterns high-lactate environment their contribution to progression cancer remain contentious. This review presents current evidence on crosstalk lactate Additionally, we provide in-depth exploration yet enigmatic mechanisms through orchestrates pathogenesis, thereby offering novel perspectives development targeted therapeutic interventions

Language: Английский

Citations

3
Lactate metabolism and lactylation in cardiovascular disease: novel mechanisms and therapeutic targets DOI Creative Commons
Han Zhang,

Jiulu Zhao,

Jizhang Yu

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Nov. 27, 2024

Cardiovascular disease (CVD) is responsible for approximately 30% of annual global mortality rates, yet existing treatments this condition are considered less than ideal. Despite being previously overlooked, lactate, a byproduct glycolysis, now acknowledged its crucial role in the cellular functions cardiovascular system. Recent studies have shown that lactate influences proliferation, differentiation, and activation immune cells through modulation post-translational protein modifications, thereby affecting development prognosis disease. Consequently, there has been notable increase interest towards drug targets targeting lactylation cells, prompting further exploration. In light swift advancements domain, review article dedicated to examining potential regulating lactylation, with aim enhancing comprehension intricate field.

Language: Английский

Citations

3
Mitochondria- and anaerobic glycolysis-targeted self-assembled copper complex nanoparticles for boosting cuproptosis-immunotherapy DOI
Hanyu Zhang,

Jing Xia,

Lingling Xie

et al.

Advanced Composites and Hybrid Materials, Journal Year: 2024, Volume and Issue: 8(1)

Published: Dec. 16, 2024

Language: Английский

Citations

3
Glutathione Induced In Situ Activation of Dual‐Locked Cuproptosis Nanoamplifier with Glycolysis Metabolism Inhibition to Boost Cancer Immunotherapy DOI
Xiaomei Wu, Shuo Zhang,

Mei Feng

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(4)

Published: Dec. 17, 2024

Interference with glycolysis metabolism not only promotes the efficient sensitization of cuproptosis, but also amplifies cytotoxic T cell functions and proliferations, thus contributing to relieve immunosuppressive tumor microenvironment. However, synergistic mechanism design multicomponent nanoformulations involving these three pathways have yet been explored. a copper-coordinated nanoassembly (designated as Cu-GM) is reported here that integrates lactate dehydrogenase inhibitor, galloflavin (GF), an immune checkpoint myricetin (MY), boost cancer cuproptosis-immunotherapy. These results suggest Cu-GM can be activated by endogenous overexpressed glutathione release Cu+, leading abnormal aggregation lipoylated proteins iron-sulfur cluster loss, which triggers proteotoxic stress cuproptosis. Meanwhile, released GF inhibits amplify cuproptosis efficacy achieves effective depletion, alleviating effects lactate. Notably, killed cells induce immunogenic death evoke anti-tumor immunity, further augmented MY-mediated blockade. Taken together, first anticancer synergy metabolism, immunotherapy presented, showcasing remarkable in vivo antitumor encouraging exploration rational multimodal treatment approach.

Language: Английский

Citations

2