Augmenting Antitumor Immune Effects through the Coactivation of cGAS-STING and NF-κB Crosstalk in Dendritic Cells and Macrophages by Engineered Manganese Ferrite Nanohybrids DOI

Heying Chen,

Dongqing Wang,

Jiahe Liu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: 17(9), P. 13375 - 13390

Published: Feb. 18, 2025

The specific activation of dendritic cells (DCs) and tumor-associated macrophages (TAMs) can activate innate adaptive immune responses to reverse the tumor immunosuppressive microenvironment. In this study, manganese ferrite nanohybrid MnFe5O8@(M1M-DOX) is synthesized cGAS-STING NF-κB crosstalk in DCs TAMs. MnFe5O8, as source Fe2+/Fe3+ Mn2+, encapsulated with a microdose doxorubicin (DOX) using an M1 macrophage cytomembrane. DOX cooperatively induce tumorous ferroptosis, triggering immunogenic cell death (ICD) that exposes antigens. release Mn2+ has intrinsic dual-immunomodulatory effects on reprogramming TAMs from M2 phenotype. Briefly, activates signaling pathway trigger STING signaling. Meanwhile, further enhances stimulates cascade-activating manner. Thus, mutually reinforcing dual prompts strong maturation TAMs, synergistically promoting infiltration T inhibit primary growth localized recurrence. This work proposes strategy for delivering immunomodulatory metal ions nanoalloy harnessing multisignaling pathways antigen-presenting (APCs) provide perspectives immunotherapy.

Language: Английский

The quest for nanoparticle-powered vaccines in cancer immunotherapy DOI Creative Commons
Zhe Sun,

Hui Zhao,

Li Ma

et al.

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

Published: Feb. 14, 2024

Abstract Despite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role preventing illness by preparing the body's adaptive and innate immune responses combat diseases. As our understanding of malignancies their connection system improves, there has been growing interest priming fight more effectively comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which shown potentiate as vaccines and/or adjuvants. In review, we comprehensively summarized immunological mechanisms while focusing specifically on applications various types nanoparticles field immunotherapy. By exploring these breakthroughs, hope identify significant challenges obstacles making nanoparticle-based adjuvants feasible clinical application. This review serves assess breakthroughs vaccinations shed light prospects potential barriers. doing so, aim inspire future immunotherapies that harness nanotechnology deliver effective targeted treatments. Graphical abstract

Language: Английский

Citations

27
Metal–Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells DOI
Yang Liu, Rui Niu, Xiaodong Zhang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12386 - 12400

Published: May 3, 2024

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability produce effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal–organic framework in situ-generate therapeutic vaccination. Once inside early endosome, alkaline overexpressed cells' membrane activates situ type I photodynamic effect of Cu-THBQ/AX for generating •O2–, catalyzes O2 H2O2 •O2– •OH via semiquinone radical catalysis Fenton-like reactions. This surge ROS endosomes triggers caspase-3-mediated proinflammatory pyroptosis activating phospholipase C. Meanwhile, can also induce oligomerization dihydrolipoamide S-acetyltransferase trigger cell cuproptosis. The production could release effectively inhibiting efferocytosis macrophages convert apoptosis cells into secondary necrosis. simultaneous induction pyroptosis, cuproptosis, necrosis converts from "cold" "hot" conditions, making it antigen pool. transformation successfully antitumor response, growth metastasis.

Language: Английский

Citations

18
Present and future of cancer nano-immunotherapy: opportunities, obstacles and challenges DOI Creative Commons
Man Wang, Fei Yu, Yuan Zhang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 18, 2025

Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause death. In recent years, immunotherapy has firmly established itself as new paradigm in cancer care that activates body's immune defense cope with cancer. Immunotherapy resulted significant breakthroughs treatment stubborn tumors, dramatically improving clinical outcome patients. Multiple forms immunotherapy, including checkpoint inhibitors (ICIs), adoptive cell therapy and vaccines, have become widely available. However, effectiveness these immunotherapies is not much satisfying. Many patients do respond disease recurrence appears unavoidable because rapidly evolving resistance. Moreover, can give rise severe off-target immune-related adverse events. Strategies remove hindrances mainly focus on development combinatorial or exploitation novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents target site considered practical approaches treatment. Nanomedicine combined offers possibility potentiate systemic antitumor immunity facilitate selective cytotoxicity against cells an effective safe manner. A myriad nano-enabled currently under investigation. Owing gaps between preclinical studies, nano-immunotherapy faces multiple challenges, biosafety nanomaterials trial design. this review, we provide overview summarize evidence indicating how nanomedicine-based increase efficacy immunotherapies. We also discuss key challenges emerged era nanotechnology-based immunotherapy. Taken together, combination drawing increasing attention, it anticipated will achieve desired success therapy.

Language: Английский

Citations

8
Cascade Carrier‐Free Nanoparticles Forming In Situ Nanovaccines for Synergistic Photothermal‐Immunotherapy of Cancer DOI
Chenlu Huang, Hanyong Wang, Xinyu Yang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(29)

Published: April 5, 2024

Abstract Rapid advances in nanotechnology have made it possible to combine photothermal therapy (PTT) with immunotherapy, enabling activate an situ vaccine effect. However, this effect is severely impeded by low antigen presentation level and highly suppressive tumor immune microenvironment (immune “cold” tumors). To overcome the obstacles, multifunctional carrier‐free nanoparticles (FCDP‐NPs) assembled from Fe 2+ , toll‐like receptor 9 agonist (CpG), cationic lipid (DOTAP) agent polydopamine are developed. After intratumoral injection, FCDP‐NPs carrying positive charge exposed under laser irradiation, which can capture tumor‐associated antigens (TAAs) generated upon post‐PTT form nanovaccines (FCD‐NPs@TAAs). The further promote cross‐presentation of TAAs, stimulate adaptive responses, shape “hot” tumors. As a result, improve survival rates elicit durable memory that remarkedly prevents metastasis, illustrating useful platform for PTT synergized immunotherapy.

Language: Английский

Citations

15
Nanocatalytic Anti‐Tumor Immune Regulation DOI
Mingyuan Li, Han Jiang,

Ping Hu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(13)

Published: Jan. 12, 2024

Abstract Immunotherapy has brought a new dawn for human being to defeat cancer. Although existing immunotherapy regimens (CAR‐T, etc.) have made breakthroughs in the treatments of hematological cancer and few solid tumors such as melanoma, therapeutic efficacy on most is still far from satisfactory. In recent years, researches tumor based nanocatalytic materials are under rapid development, significant progresses been made. Nanocatalytic medicine demonstrated be capable overcoming limitations current clinicnal by using toxic chemodrugs, exhibits highly attractive advantages over traditional therapies, enhanced sustained durable catalytic activity, remarkably reduced harmful side‐effects without so on. Most recently, introduced immune‐regulation disease treatments, especially, immunoactivation therapies. This article presents immune‐response activations medicine‐initiated chemical reactions immunotherapy, elucidates mechanism medicines regulating anti‐tumor immunity. By reviewing research progress emerging field, this review will further highlight great potential broad prospects nanocatalysis‐based immune‐therapeutics.

Language: Английский

Citations

14
Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis–Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation DOI
Weiran Cao, Xue Zhang,

Yaxuan Feng

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 17267 - 17281

Published: June 13, 2024

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role maintaining redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing cytotoxicity and rendering them less effective. In this study, we combined erastin, GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, effectively disrupt reverse chemotherapy resistance. Therefore, efficient ferroptosis apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, employed small interfering RNA targeting PD-L1 (siPD-L1) as third agent block immune-checkpoint recognition CD8

Language: Английский

Citations

14
Engineering customized nanovaccines for enhanced cancer immunotherapy DOI Creative Commons

JinYu Guo,

Changhua Liu, Zhaoyang Qi

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 36, P. 330 - 357

Published: March 11, 2024

Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized through modification or functionalization has emerged a promising approach. These tailored not only enhance antigen presentation, but also effectively modulate immunosuppression within the microenvironment. Specifically, they are distinguished by diverse sizes, shapes, charges, structures, unique physicochemical properties, along with ligands. features facilitate lymph node accumulation activation/regulation immune cells. This overview bespoke underscores both prophylactic therapeutic applications, offering insights into future development role cancer immunotherapy.

Language: Английский

Citations

13
Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties DOI Creative Commons
Eduardo Angulo-Elizari, Andreina Henriquez-Figuereo, Cristina Morán-Serradilla

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116249 - 116249

Published: Feb. 23, 2024

Cancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they not always effective or safe, often failing to achieve the desired results. This is why it necessary continue search new therapies. One strategies obtaining antitumor drugs use 1,4-naphthoquinone as scaffold synthetic natural products activity. review focuses on compiling studies related activity its derivatives over last 10 years. The work describes main naphthoquinones classifies based structural modifications made scaffold. Additionally, formation metal complexes using ligand considered. After thorough review, 197 compounds potent biological against cancer have been classified according their chemical structures mechanisms action described.

Language: Английский

Citations

11
Tumor Microenvironment‐Activatable Metal‐Phenolic Nanoformulations for Ultrasound‐Boosted Ferroptosis through Triple Regulatory Pathways DOI

Zhendong Liu,

Sainan Liu,

Bin Liu

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(44)

Published: July 16, 2024

Abstract Despite its effectiveness in exterminating tumor cells, ferroptosis is seriously hampered by the high expression of antioxidant glutathione (GSH) and inadequacy endogenous H 2 O tumors. Herein, metal‐phenolic nanoformulations (FNCP NFs) composed sonosensitizer Chlorin e6 (Ce6), phenolic GSH consumer naphthazarin, Fe 3+ , followed modification PEG2000, are strategically designed fabricated for ultrasound‐boosted cells through triple regulatory pathways. The carrier‐free FNCP NFs can rapidly dissociate under microenvironment response with assistance ultrasound, releasing 2+ Ce6, naphthazarin. Ce6 capable producing singlet oxygen ( 1 ) hydroxyl radicals · OH) ultrasound‐activated sonodynamic therapy Fenton reaction‐mediated chemodynamic (CDT), respectively, which not only induce apoptotic cell death but also lead to effective accumulation lipid peroxidation (LPO), resulting ferroptosis. Meanwhile, released naphthazarin self‐cycling valence alternations /Fe promote significant decrease intracellular contents, further inducing inactivation peroxidase 4 (GPX4) up‐regulation LPO levels, eventually realizing synergistically enhanced This facile feasible design versatile offers a new strategy effectively improving efficiency multimodal cancer therapies.

Language: Английский

Citations

9
Fe/Mo‐Based Lipid Peroxidation Nanoamplifier Combined with Adenosine Immunometabolism Regulation to Augment Anti‐Breast Cancer Immunity DOI Open Access
Qinyanqiu Xiang, Xue Yang, Zhi‐Qi Zhang

et al.

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

Published: Jan. 6, 2025

Immunogenic cell death (ICD)-mediated immunization strategies have great potential against breast cancer. However, traditional neglect the increase in immunosuppressive metabolite, adenosine (ADO), during ICD, leading to insufficient therapeutic outcomes. In this study, it is found that A2A receptor (A2AR) significantly expressed cancer and positively associated with regulatory T (Treg) cells. Herein, a strategy combining Fe/Mo-based lipid peroxidation (LPO) nanoamplifiers A2AR blockade reported maximize ICD-mediated anti-tumor immunity. This LPO nanoamplifier causes explosion by Fe (II)-mediated Fenton reaction Mo(V)-mediated Russell mechanism. Subsequently, elicits ICD magnification of tumor cells inducing multiple regulated patterns ferroptosis, apoptosis, necroptosis. Additionally, antagonist (SCH58261), an immunometabolic checkpoint blocker, relieve ADO-related immunosuppression, amplify immunological effects, elicit immune memory responses. robust immunity observed primary, distant, pulmonary metastatic, recurrent tumors. study provides novel for optimizing immunotherapy highlights benefits enhance immunotherapy.

Language: Английский

Citations

1