Cuproptosis: an emerging domain for copper-based nanomaterials mediated cancer therapy DOI
Fan Zhao,

Zhuangzhuang Zhao,

Hao Gao

et al.

MedMat., Journal Year: 2024, Volume and Issue: 1(2), P. 74 - 94

Published: Dec. 1, 2024

Cuproptosis, a newly discovered copper-dependent mode of cell death, has received extensive attention in the field cancer therapy due to its specific activation pathway. Rapid accumulation large amounts copper ions within cells achieve overload is key activating cuproptosis. Advanced nanotechnology offers considerable promise for delivering cells, which copper-based nanomaterials have been proposed evoke cuproptosis-mediated therapy. However, it still great challenge induce specifically tumors and efficiently activate subsequent cuproptosis-related molecular pathways. Therefore, necessary summarize strategies used effectively or amplify cuproptosis based on currently developed nanomaterials, providing ideas design future. In this review, that can be are systematically classified selection. Subsequently, sensitization using provided therapeutic efficiency. Meanwhile, combination therapies maximizing treatment efficacy delineated. Ultimately, remaining challenges feasible future directions use tumor also discussed.

Language: Английский

Spatial Isolation of Single Copper(I) Sites for Cascade Enzyme‐Like Catalysis and Simultaneous Ferroptosis/Cuproptosis Boosted Immunotherapy DOI Creative Commons
Yuanyuan Zhang,

Shengnan Ya,

Jingnan Huang

et al.

Exploration, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

ABSTRACT Nanozyme‐based immunogenic cell death (ICD) inducers that effectively induce a strong immune response via enzyme‐like process have attracted great attention, but how to ensure controllable active sites and maximize site utilization remains problem. Here, we report structurally well‐defined highly functional single‐site copper(I) nanomodulators termed CuNTD, constructed by precisely anchoring atomically dispersed self‐assembly S‐Cu(I)‐S onto two‐dimensional Ti 3 C 2 surface. Leveraging Cu + with higher catalytic efficiency than 2+ , CuNTD generates reactive oxygen species (ROS) storms through photothermal‐enhanced cascade catalysis, further inducing mitochondrial dysfunction, ferroptosis cuproptosis. Multifunctional triggers ICD cascade‐regulatory pathways of photothermal‐amplified ROS storms, cuproptosis ferroptosis, promoting dendritic maturation while reducing monotherapies side effects resistance. In vivo, combined FDA‐approved immunoadjuvants significantly prolong the survival mice. With its demonstrated biosafety high as an inducer, this study provides promising framework for advancing augmented tumor immunotherapy significant clinical potential.

Language: Английский

Citations

0
Injectable Magnetic-Nanozyme Based Thermosensitive Hydrogel for Multimodal DLBCL Therapy DOI Creative Commons

Min Yan,

Jingcui Peng,

Haoan Wu

et al.

Gels, Journal Year: 2025, Volume and Issue: 11(3), P. 218 - 218

Published: March 20, 2025

Diffuse large B-cell lymphoma (DLBCL), accounting for 31% of non-Hodgkin lymphomas, remains recalcitrant to conventional therapies due chemoresistance, metastatic progression, and immunosuppressive microenvironments. We report a novel injectable Fe3O4@DMSA@Pt@PLGA-PEG-PLGA hydrogel system integrating magnetothermal therapy (MHT), chemodynamic (CDT), immunomodulation. Under alternating magnetic fields (AMF), the achieves rapid therapeutic hyperthermia (50 °C within 7 min) while activating pH/temperature-dual responsive peroxidase (POD) -like activity in Fe3O4@DMSA@Pt nanoparticles. Catalytic efficiency under tumor-mimetic conditions was significantly higher than Fe3O4@DMSA controls, generating elevated reactive oxygen species (ROS). Flow cytometry revealed 75.9% apoptotic cell death A20 cells at 50 °C, surpassing CDT alone (24.5%). Importantly, this dual mechanism induced immunogenic (ICD) characterized by 4.1-fold CRT externalization, 68% HMGB1 nuclear depletion, 40.74 nM ATP secretion. This triggered robust dendritic maturation (92% CD86+/CD80+ DCs comparable LPS controls) T activation (16.9% CD25+/CD69+ ratio, 130-fold baseline). Our findings validate potential magnetothermal-chemodynamic synergy DLBCL treatment, paving way innovative multi-mechanism strategies against with clinical translation prospects.

Language: Английский

Citations

0
Dual-Regulated Biomimetic Nanocomposites For Promoted Tumor Photodynamic Immunotherapy DOI
Li Liao, Yufei Liu, Xianhai Li

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Effective tumor immunotherapy is hindered by an immunosuppressive microenvironment (TME), especially in triple-negative breast cancer. Though phototherapy could induce immunogenic cell death (ICD) to increase antitumor immunity, the simultaneous upregulation of indoleamine 2,3-dioxygenase (IDO) induces negative immunomodulatory effect termed as "immune-metabolism" loop compromise immunotherapeutic efficacy. Herein, we developed IMMGP consisting biomimetic IND-Mn@PM (IDP) and ICG-MnO2@PM (IMP), which combines phototherapy-induced ICD metabolic reprogramming solve dilemma. During light-on phase, IMP effectively kills cancer cells with potent photodynamic ROS generation assistance MnO2-produced oxygen reverse TME. In light-off Mn2+ (from IDP MnO2-based redox reaction) elicits a Fenton-like reaction relay generation, further orchestrated continuous exhaustion intratumoral GSH conversion Mn3+ Mn2+, promotes dendritic maturation. Moreover, released indoximod (IND) downregulated IDO inhibit kynurenine metabolism, reinvigorates T cell-mediated immunity. Collectively, amplifies immune response breaking sustaining "immunologically hot" state after phototherapy, thus leading nearly complete inhibition (94.25%). Thus, IMMGP-mediated dual-phase offers novel approach nanomedicine.

Language: Английский

Citations

0
Inhibiting Chemotherapy Immune Tolerance and Reversing Tumor Microenvironment by Macrophage‐Targeted Nanohybrid Systems for Enhancing Tumor Chemo‐Immunotherapy DOI

You‐Teng Qin,

Zhi‐Yong Rao,

Jiaxin An

et al.

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

Published: April 7, 2025

Abstract Chemotherapy combined with immunotherapy (chemo‐immunotherapy) has emerged as a critical strategy in tumor treatment. However, chemotherapy induced immune tolerance and the immunosuppressive microenvironment limit its effectiveness. Secondary necrosis can generate additional immunogenic substances, enhancing immunogenicity of cells, but macrophage‐mediated clearance apoptotic cells inhibits occurrence secondary necrosis. In this study, tumor‐associated macrophage (TAM)‐targeting nanohybrid system, SC@P@U, is designed by combining poly (lactic‐co‐glycolic acid) (PLGA)‐loaded MerTK inhibitor UNC2025 (P@U) saccharomyces cerevisiae‐derived β‐glucan (SC shell). This system specifically targets TAMs, preventing them from clearing inhibiting their polarization into immune‐suppressive M2 macrophages. More importantly, it activates STING pathway, further stimulating dendritic initiating T cell‐mediated responses. vivo experiments demonstrated that when paclitaxel (PTX), significantly suppressed growth, activated anti‐tumor immunity, and, used conjunction checkpoint αPD‐1, markedly enhanced effect. overcomes traditional chemo‐immunotherapy, reverses microenvironment, offers promising approach to

Language: Английский

Citations

0
Guanidinium/Phenyl-Rich Amphiphilic Cationic Polymer for Efficient Cytosolic Protein Delivery and Cancer Immunotherapy DOI
Nana Feng, Xianghui Cao, Jian Xiao

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Protein drugs have garnered increasing attention in biomedical applications due to their high specificity for target receptors and minimal side effects. However, the macromolecular hydrophilic nature of proteins severely hinders ability penetrate cell membranes, restricting intracellular applications. Herein, we present an innovative amphiphilic cationic polymer, p(PG420-co-HP15), capable forming stable nanoparticles with diverse facilitating efficient cytosolic delivery. By incorporating guanidinium phenyl ligands, p(PG420-co-HP15) effectively complexes various via hydrogen bonding, salt bridges, hydrophobic π-π interactions. Meanwhile, ligands further enhance cellular uptake promote endosomal escape by inducing membrane perturbations, likely through disruption phospholipid packing increased fluidity. Consequently, enables delivery 6 proteins, each unique molecular weights, isoelectric points, biological functions across different lines, surpassing commercial reagent PULSin efficiency. Furthermore, constructed nanovaccines ovalbumin (OVA), significantly boosting T cell-mediated antitumor immunity a B16-OVA melanoma mouse model. These findings emphasize potential as versatile protein platform broad disease treatment, vaccine development, research.

Language: Английский

Citations

0
Efficient chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle as “in situ” vaccine integrated tumor ICD and immunoagonist DOI Creative Commons

Yunfei Han,

Mingxia Jiang,

Yanju Sun

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Immunotherapy has unprecedentedly opened up a series of neoteric tactics for cancer treatment. As burgeoning approach, chemo-immunotherapy innovatively expanded the accomplishments conventional chemotherapeutic agents governing. An efficacious leveraging minimalist electrostatic complex nanoparticle (NP) integrated tumor immunogenic cell death (ICD) and immunoagonist was developed as watertight "in situ" vaccine therapy through convenient intratumoral administration with minimized systemic toxicity. Chemical-modified pH-sensitive cis-aconityl-doxorubicin (CAD) immunoadjuvant unmethylated cytosine-phosphate-guanine (CpG) were co-packaged by polycationic polyethylenimine (PEI) though electrostatic-interaction to construct PEI/CpG/CAD NP. By injection, this positively charged NP could be detained at site endocytosed cells effortlessly. Then, doxorubicin released cis-aconityl cleavage induced endosomal-acidity further triggered ICD, moribund release damage-associated molecular patterns (DAMPs) recruit dendritic (DCs). Meanwhile, entire debris derived into diversified antigens cooperated immunostimulatory CpG excite DC maturation activated comprehensive antitumor immunity. Prominent suppression achieved in aggressive mouse melanoma model, which verified feasibility effectiveness CAD/CpG-codelivered This study provided promising paradigm potent chemo-immunotherapy.

Language: Английский

Citations

2
Supramolecular Nano‐Tracker for Real‐Time Tracking of Drug Release and Efficient Combination Therapy DOI Creative Commons
Xi Chen, Fangyuan Chen, Yi Lü

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 28, 2024

Real-time tracking of drug release from nanomedicine in vivo is crucial for optimizing its therapeutic efficacy clinical settings, particularly dosage control and determining the optimal window. However, most current real-time systems require a tedious synthesis purification process. Herein, supramolecular nano-tracker (SNT) capable based on non-covalent host-guest interactions presented. By integrating multiple cavities into single nanoparticle, SNT achieves co-loading drugs probes while efficiently quenching photophysical properties probe through complexation. Moreover, readily degraded under hypoxic tumor tissues, leading to simultaneous fluorescence recovery probes. With this spatial temporal consistency loading quenching, as well recovery, successfully (Pearson r = 0.9166, R

Language: Английский

Citations

2
A thermoresponsive metabolic nanomodulator for achieving photochemotherapy-sensitized cancer immunotherapy DOI

Shun‐Yu Wu,

Xiao-Yu Zhu,

Xinping Zhang

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 155593 - 155593

Published: Sept. 1, 2024

Language: Английский

Citations

1
Current status of nanoparticle-mediated immunogenic cell death in cancer immunotherapy DOI
Tuan Hiep Tran, Thi Thu Phuong Tran

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113085 - 113085

Published: Sept. 13, 2024

Language: Английский

Citations

1
Dual‐Activatable Nano‐Immunomodulator for NIR‐II Fluorescence Imaging‐Guided Precision Cancer Photodynamic Immunotherapy DOI Creative Commons

Shanchao Diao,

Zhifan Zhang, Sijun Zhao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Photodynamic immunotherapy which combines photodynamic therapy with has become an important and effective method for the treatment of cancer. However, most cancer immunotherapeutic systems are not able to achieve precise release immunomodulators, resulting in systemic side effects poor patient outcomes. Herein, a dual‐activatable nano‐immunomodulator (DIR NP), both its effect agonist can be activated under specific stimuli, is reported precision immunotherapy. The DIR NP self‐assembled from R848‐conjugated amphiphilic polymer (mPEG‐TK‐R848) hydrophobic oxidized bovine serum albumin (BSA‐SOH)‐conjugatable photosensitizer (DIR). NPs may generate small amount 1 O 2 808 nm laser irradiation, leading cleavage thioketal (TK) moiety R848 DIR. released conjugate tumor‐overexpressed BSA‐SOH, improving efficiency NIR‐II fluorescence signal. Such improvement further enhance cargoes upon irradiation. induces immunogenic cell death (ICD) immune factors maturation dendritic cells inhibiting growth primary distant tumors eliminating lung metastasis. Therefore, this study provides intelligent regulation tumor

Language: Английский

Citations

0