Photo-Thermally Controllable Tumor Metabolic Modulation to Assist T Cell Activation for Boosting Immunotherapy DOI Creative Commons
Jun Ma, Lixin Hua, Yinxing Zhu

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 11181 - 11194

Published: Nov. 1, 2024

Background: Glycolysis is crucial for tumor cell proliferation, supporting their energy needs and influencing the microenvironment (TME). On one hand, increased lactate levels produced by glycolysis acidifies TME, inhibiting T activity. other promotes expression of PD-L1 through various mechanisms, facilitating immune evasion. Therefore, controlled modulation in cells to subsequently improve holds significant implications clinical cancer treatment regulation. Methods: To reverse immunosuppressive caused reduce escape, we developed a photo-thermal-controlled precision drug delivery platform regulate metabolism aid activation cells, thereby enhancing immunotherapy. First, hollow mesoporous Prussian blue (HPB) was prepared, inhibitor 3-bromopyruvate (3-BrPA) encapsulated within HPB using phase-change material 1-tetradecanol, resulting B/T-H. This product then modified with membranes obtain photo-thermal controllable regulator (B/T-H@Membrane, B/T-HM). Results: Due excellent loading properties HPB, upon reaching tumor, B/T-HM can rapidly heat under 808 nm irradiation, causing 1-tetradecanol transition liquid phase release 3-BrPA, which effectively inhibits HK2 pathway, reducing decreasing production, downregulating expression. In synergy αPD-1, this photo-thermally metabolic-immune therapy activates eliminate tumor. Conclusion: response changes metabolism, precision-controlled successfully developed. reshapes microenvironment, providing new approach cell-based It also opens avenues therapy. Keywords: controllable, glycolysis, PD-L1, cell,

Language: Английский

Copper‐Based Bio‐Coordination Nanoparticle for Enhanced Pyroptosis‐Cuproptosis Cancer Immunotherapy through Redox Modulation and Glycolysis Inhibition DOI Open Access

Ju‐E Cun,

Ziyun He,

Fan Xi

et al.

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

Published: Jan. 5, 2025

Copper-based nanoparticles have garnered significant interest in cancer therapy due to their ability induce oxidative stress and cuproptosis cells. However, antitumor effectiveness is constrained by the dynamic redox balance metabolic shift between phosphorylation glycolysis. Here, a polydopamine-coated copper-α-ketoglutaric acid (α-KG) coordination polymer nanoparticle (CKPP) designed for combined pyroptosis-cuproptosis immunotherapy amplifying reactive oxygen species (ROS) production regulating cellular metabolism. The intracellular imbalance achieved through synergistic effects of α-KG-induced mitochondrial reprogramming, photothermally enhanced superoxide dismutase-like activity polydopamine, glutathione depletion copper ions. multifaceted modulation results substantial increase ROS levels, triggering subsequent pyroptosis Furthermore, α-KG shifts metabolism from glycolysis phosphorylation, thereby enhancing induced combination dyshomeostasis inhibition potent enhancement pyroptosis-cuproptosis-mediated therapy. In murine model colorectal cancer, CKPP exhibited remarkable anticancer effect, achieving tumor rate 96.3% complete eradication two out five cases. Overall, this bio-engineered metal-organic nanocomposite demonstrates potential treating immunotherapy.

Language: Английский

Citations

2
Microneedle patch-involved local therapy synergized with immune checkpoint inhibitor for pre- and post-operative cancer treatment DOI
Yue Yin, Lu Tang,

Yuqi Cao

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 678 - 695

Published: Jan. 24, 2025

Language: Английский

Citations

1
Remodeling tumor microenvironment using prodrug nMOFs for synergistic cancer therapy DOI Creative Commons
Jun-Liang Dong,

Jin-Dong Ding,

Shuang Luo

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 19, 2025

Metal–organic frameworks (MOFs) hold tremendous potential in cancer therapy due to their remarkable structural and functional adaptability, enabling them serve as nanocarriers for biopharmaceuticals nanoreactors organizing cascade bioreactions. Nevertheless, MOFs are predominantly utilized biologically inactive carriers most cases. Developing nanoscale prodrug suitable biomedical applications remains a huge challenge. In this study, we have designed novel nano-MOFs (nMOFs, named DCCMH) using metformin (Met) α-cyano-4-hydroxycinnamic acid (CHCA) ligands coordination self-assembly with CuCl2, followed by loading of doxorubicin (DOX) surface modification hyaluronic (HA). Upon internalization cells, DCCMH releases Cu2+/+, CHCA, Met, DOX response high levels glutathione (GSH) hydrogen peroxide (H2O2) within the tumor microenvironment (TME); Cu+ catalyzes conversion H2O2 ·OH via Fenton reaction while it was oxidized Cu2+, which subsequently further de-consumed GSH; CHCA induces decrease intracellular pH promotes reactions inhibiting lactate efflux; Met up-regulates tyrosine kinase activity enhances chemotherapy DOX. With ability synergistically combine chemo/chemodynamic (CT/CDT) remodel TME, NPs inhibit murine hepatoma effectively. This study presents feasible strategy fabricating nMOFs capable remodeling TME improve efficacy through synergistic therapy.

Language: Английский

Citations

1
Metal-based nanomedicines and their immunoregulatory effects DOI
Hang Liu, Mingjing Cao, Chunying Chen

et al.

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Engineered nano-aluminum adjuvant for cancer immunotherapy: Progress, challenges and opportunities towards preclinical/clinical application DOI Creative Commons
Chong Gao, Jianping Jiang, Jing Zhao

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 519, P. 216109 - 216109

Published: Aug. 1, 2024

Immunotherapy is a promising strategy to inhibit the progression of solid tumors. However, current vaccine adjuvants represented by aluminum adjuvant (Alum) fail tumor antigens initiate effective T cell immunity. Despite efforts have been made optimize physical characteristics Alum, lack specific immunostimulatory functions still results in their inability effectively induce cytotoxic immune responses. Encouragingly, an iterative layered double hydroxide (LDH) nano‑aluminum (NanoAlum) re-engineered from clinical AlOOH Alum and Mg(OH)2 antacid has shown efficacy evoking both potent humoral cellular Notably, it can also serve as microenvironmental immunomodulator reshape aberrant physicochemical attributes microenvironment. Interestingly, highly flexible crystal structure chemical composition offer variety LDH-based candidates (NanoMAlum) doping with body essential nutritional metal ions (M), which show great potential amplify immunotherapy. In this review, we summarize development progress LDH NanoAlum its variants NanoMAlum for cancer By rethinking challenges that hindered preclinical/clinical application, charted research pathway based on engineered organoids accelerate applications these NanoMAlums review.

Language: Английский

Citations

7
Potentiated Calcium Carbonate with Enhanced Calcium Overload Induction and Acid Neutralization Capabilities to Boost Chemoimmunotherapy against Liver Cancer DOI

Liyun Zheng,

Yiming Ding,

Shiji Fang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(40), P. 27597 - 27616

Published: Sept. 29, 2024

Unfavorable phenotypes characterized by low immunogenicity and acidity within the tumor microenvironment (TME) contribute to immunosuppression therapeutic resistance. Herein, we rationally synthesized a multifunctional nanoregulator encapsulating DOX erianin into calcium carbonate (CaCO

Language: Английский

Citations

6
19F MRI/CEUS Dual Imaging‐Guided Sonodynamic Therapy Enhances Immune Checkpoint Blockade in Triple‐Negative Breast Cancer DOI Creative Commons

Qiu Chen,

Hong Xiao, Lijun Hu

et al.

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

Published: July 25, 2024

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic for bimodal imaging-guided sonodynamic therapy (SDT) developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) TNBC. In acidic tumor microenvironment (TME), LP@PFH@HMME undergoes "nano-to-micro" transformation due pH-responsive lipid fusion, makes droplets much more sensitive ultrasound (US) contrast-enhanced (CEUS) SDT studies. The demonstrates robust ability through fluorine-19 magnetic resonance (

Language: Английский

Citations

5
Near Infrared‐Fluorescent Dinuclear Iridium(III) Nanoparticles for Immunogenic Sonodynamic Therapy DOI Open Access
Dongsheng Tang,

Minhui Cui,

Bin Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(38)

Published: July 31, 2024

Abstract Dinuclear iridium(III) complexes activated by light‐inducible spatiotemporal control are emerging as promising candidates for cancer therapy. However, broader applications of current light‐activated dinuclear limited the ineffective tissue penetration and undesirable feedback on guidance activation. Here, an ultrasound (US) triggered near infrared‐fluorescent nanoparticle, NanoIr, is first reported to precisely spatiotemporally inhibit tumor growth. It demonstrated that reactive oxygen species can be generated NanoIr upon exposure US irradiation (NanoIr + US), thereby inducing immunogenic cell death. When combined with cisplatin, elicits synergistic effects in patient‐derived xenograft mice models ovarian cancer. This work provides a design nanoparticles sonodynamic

Language: Английский

Citations

4
Next-generation aluminum adjuvants: Immunomodulatory layered double hydroxides NanoAlum reengineered from first-line drugs DOI Creative Commons
Zhenwei Su, Hamza Boucetta, Jiahui Shao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(11), P. 4665 - 4682

Published: Sept. 14, 2024

Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), widely antacid, has emerged as novel class potent nano-aluminum (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility adjuvanticity both responses. In this review, we summarize compare advantages disadvantages Alum NanoAlum these properties performance adjuvants. Moreover, propose key features ideal demonstrate that LDH promising candidate summarizing its current progress immunotherapeutic cancer treatments. Finally, conclude review offering our integrated perspectives about remaining challenges future directions NanoAlum's application preclinical/clinical settings.

Language: Английский

Citations

4
Tumor microenvironment–responsive and modulatory manganese-based nanoenzyme for enhanced tumor immunotherapy DOI Creative Commons

Qi Yang,

Qiong Wu, Haiyan Liu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

The characteristics of the tumor microenvironment (TME) have a close and internal correlation with effect cancer immunotherapy, significantly affecting progression metastasis cancer. rational design nanoenzymes that possess ability to respond regulate TME is driving new direction in catalytic immunotherapy. In this study, we designed multifunctional manganese (Mn)-based nanoenzyme responsive acidic pH overxpressed H2O2 at site holds capability modulating hypoxic immunosuppressive for synergistic anti-tumor photothermal/photodynamic/immunotherapy. We found artificial promoted peroxidase-like catalase-like activities catalyzed in-situ decomposition H2O2, metabolic waste product TME, into ∙OH O2, resulting ROS burst killing tumors relieving enhance therapy. Besides photothermal enhancement burst-induced immunogenic cell death, combination Mn2+ released from Mn-based programmed death-ligand 1 blockade triggered significant immune response. A remarkable vivo therapeutic was achieved effective inhibition primary growth lung metastasis. Therefore, TME-responsive offers safe efficient platform reversing achieving

Language: Английский

Citations

0