Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD‐L1 for Enhanced Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(22)

Published: March 14, 2023

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces death. However, existing are small molecules with short blood half-life making it hard enough cells. Herein, reactive oxygen species (ROS)-sensitive polymer (PHPM) designed, used co-encapsulate elesclomol (ES) and form nanoparticles (NP@ESCu). After entering ES Cu, triggered by excessive intracellular ROS, readily released. work in concerted way not only kill cells cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu efficiently cuproptosis investigated. addition, change transcriptomes treated explored RNA-Seq. vivo, found mice model subcutaneous bladder cancer, reprograming tumor microenvironment. Additionally, further combined anti-programmed protein ligand-1 antibody (αPD-L1). This study provides first report combining nanomedicine can αPD-L1 for enhanced therapy, thereby providing novel strategy future therapy.

Language: Английский

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Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Language: Английский

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Efficient Delivery of Lomitapide using Hybrid Membrane‐Coated Tetrahedral DNA Nanostructures for Glioblastoma Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(24)

Published: April 3, 2024

Abstract Glioblastoma (GBM) is the most aggressive and prevalent primary malignant tumor of central nervous system. Traditional chemotherapy has poor therapeutic effects significant side due to drug resistance, natural blood‐brain barrier (BBB), nonspecific distribution, leading a lack clinically effective drugs. Here, 1430 small molecule compounds are screened based on high‐throughput screening platform novel anti‐GBM drug, lomitapide (LMP) obtained. Furthermore, bionic nanodrug delivery system (RFA NPs) actively targeting GBM constructed, which mainly consists tetrahedral DNA nanocages (tFNA loaded with LMP as core folate‐modified erythrocyte–cancer cell–macrophage hybrid membrane (FRUR) shell. FRUR camouflage conferred unique features tFNA NPs, including excellent biocompatibility, improved pharmacokinetic profile, efficient BBB permeability, ability. The results show that RFA NPs exhibited superior specific activities, reduced off‐target delivery, prolonged lifespan, negligible in tumor‐bearing mice. This study combines biomimetic technology provide theoretical practical basis for development optimization clinical treatment strategies treatment.

Language: Английский

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Tetrahedral DNA Nanostructure with Interferon Stimulatory DNA Delivers Highly Potent Toxins and Activates the cGAS‐STING Pathway for Robust Chemotherapy and Immunotherapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(8)

Published: Dec. 9, 2022

Tumor metastases and reoccurrences are considered the leading cause of cancer-associated deaths. While highly efficient treatments for eradication primary tumors have been developed, treatment secondary or metastatic remains poorly accessible. Over past years, compounds that intervene through cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling pathway against tumor emerged with potential clinical development. stimulatory DNAs demonstrated activation this pathway, these associated poor bioavailability, stability, cancer selectivity, hindering their use therapeutic applications. Herein, encapsulation a potent chemotherapeutic platinum(II) complex incorporation DNA strands cGAS-STING into multimodal tetrahedral nanostructures (84bp-TDNISD/56MESS ) combined chemotherapy immunotherapy is reported. It found 84bp-TDNISD/56MESS can work as not only drug delivery carrier toxins, but also an immunostimulant agent activate STING antitumor immune responses. In mouse breast model, nanostructure to nearly fully eradicate well secondary/metastatic tumors, hence demonstrating its translational value.

Language: Английский

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Alendronate Triggered Dual‐Cascade Targeting Prodrug Nanoparticles for Enhanced Tumor Penetration and STING Activation of Osteosarcoma

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(49)

Published: Sept. 3, 2023

Abstract The complex physiological environment in bone tissue poses a challenge to the efficient delivery of chemotherapeutic agents for osteosarcoma (OS) treatment; hence, an drug system designed OS is highly desired. Herein, alendronate (Ale)‐based cationic platinum prodrug nanoparticles (Ale NP) are developed, which exhibit cascade responsiveness tumor microenvironment. With Ale triggered targeting and charge reversal effects, NP demonstrates superior capacity achieving deep penetration into dense tissues. Furthermore, can induce dendritic cell (DC) maturation via activation cyclic GMP‐AMP synthase‐stimulator interferon genes (cGAS‐STING) pathway using drugs. potent phenanthridine (Pt(II)) be released presence overexpressed glutathione (GSH) cells, thereby dual‐targeted drugs OS. Notably, not only effectively eliminates internal region but also acts as STING agonist reverse suppressive microenvironment Overall, Ale‐triggered dual‐cascade significantly improve OS, hence paving promising avenue clinical treatment

Language: Английский

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NIR-II light evokes DNA cross-linking for chemotherapy and immunogenic cell death

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 160, P. 198 - 210

Published: Feb. 13, 2023

Language: Английский

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Fibrous dressing containing bioactive glass with combined chemotherapy and wound healing promotion for post-surgical treatment of melanoma

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 149, P. 213387 - 213387

Published: March 16, 2023

Language: Английский

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Platinum-based drugs in cancer treatment: Expanding horizons and overcoming resistance

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1301, P. 137366 - 137366

Published: Dec. 19, 2023

Language: Английский

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Recent updates in nanoscale delivery systems of platinum(IV) antitumor prodrugs

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 508, P. 215774 - 215774

Published: March 18, 2024

Language: Английский

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Recent advancements in Nanotechnology-Mediated Platinum-Based cancer therapy

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 508, P. 215796 - 215796

Published: March 17, 2024

Language: Английский

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