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

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

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Remodeling tumor microenvironment using prodrug nMOFs for synergistic cancer therapy

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

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Engineered nano-aluminum adjuvant for cancer immunotherapy: Progress, challenges and opportunities towards preclinical/clinical application

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

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

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

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Microneedle patch-involved local therapy synergized with immune checkpoint inhibitor for pre- and post-operative cancer treatment

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

Published: Jan. 24, 2025

Language: Английский

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Cancer Immunotherapy Based on the Bidirectional Reprogramming of the Tumor Microenvironment by a “Brakes Off/ Step on the Accelerator” Core‐Shell Manganese Phosphate/siPD‐L1 Modulator

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

Published: Feb. 9, 2025

ABSTRACT The insufficient infiltration and functional inhibition of CD8 + T cells due to tumor microenvironment (TME) are considered enormous obstacles anti‐tumor immunotherapy. Herein, a pH‐responsive core‐shell manganese phosphate nanomodulator co‐loading siPD‐L1 Mn 2+ into nanoparticles coated with hyaluronic acid was prepared, which aimed at the bidirectional reprogramming microenvironment: (1) “Brakes off,” restoring function by knockdowning PD‐L1 expression cells; (2) “Step on accelerator,” promoting in tumors tissue based multidimensional immune effects (immunogenic cell death induced enhancing cGAS‐STING pathway, proliferation maturation relative cells). Additionally, this strategy could induce macrophage polarization inhibit regulatory site. This work provided reprogram TME for an enhanced comprehensive effect triple negative breast cancer, offers robust method immunotherapy future clinical applications.

Language: Английский

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Metal-based nanomedicines and their immunoregulatory effects

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

Published: Jan. 1, 2025

Language: Английский

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Regulation of cancer-associated fibroblasts for enhanced cancer immunotherapy using advanced functional nanomedicines: an updated review

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

Published: March 4, 2025

The tumor microenvironment (TME) is a complex and dynamic ecosystem that plays critical role in cancer progression. It comprises various cell types, including immune cells, stromal cells. Among these, cancer-associated fibroblasts (CAFs) represent heterogeneous population with diverse origins, phenotypes, functions. Activated CAFs secrete multiple factors promote growth, migration, angiogenesis, contribute to chemoresistance. Additionally, extracellular matrix (ECM) components, such as collagen, which form physical barrier hinders the penetration of chemotherapeutic immunotherapeutic agents. This ECM also influences infiltration, impeding their ability effectively target As result, modulating activity has emerged promising strategy enhance efficacy immunotherapy. Nano-delivery systems, constructed from nanomaterials high targeting specificity biocompatibility, offer compelling approach deliver therapeutic agents or immunomodulatory directly CAFs. modulation can alter CAF function, reduce tumor-promoting effects, thereby improve outcomes review provides an in-depth exploration functions, interactions within TME, particularly context suppression. Furthermore, it discusses potential applications functional nanocarrifers enhancing effectiveness immunotherapy, highlighting significant progress nanotechnology this area.

Language: Английский

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Next-generation aluminum adjuvants: Immunomodulatory layered double hydroxides NanoAlum reengineered from first-line drugs

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

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

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

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