Nature Nanotechnology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 19, 2024
Язык: Английский
Coordination Chemistry Reviews, Год журнала: 2023, Номер 494, С. 215332 - 215332
Опубликована: Июль 17, 2023
Язык: Английский
Процитировано
46
Advanced Science, Год журнала: 2023, Номер 11(9)
Опубликована: Дек. 14, 2023
Abstract Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and cartilage destruction. The severity of OA highly associated with the imbalance between M1 M2 synovial macrophages. In this study, novel strategy designed to modulate macrophage polarization reducing intracellular reactive oxygen species (ROS) levels regulating mitochondrial function. A ROS‐responsive polymer synthesized self‐assemble astaxanthin autophagy activator rapamycin form nanoparticles (NP@Poly RHAPM ). vitro experiments show that NP@Poly significantly reduced ROS levels. Furthermore, restored membrane potential, increased glutathione (GSH) levels, promoted autophagy, hence successfully repolarizing macrophages into phenotype. This repolarization enhanced chondrocyte proliferation vitality while inhibiting apoptosis. vivo utilizing an anterior cruciate ligament transection (ACLT)‐induced mouse model revealed anti‐inflammatory cartilage‐protective effects , effectively mitigating progression. Consequently, findings suggest intra‐articular delivery nanocarrier systems holds significant promise as potential effective therapeutic for treatment.
Язык: Английский
Процитировано
43
Advanced Science, Год журнала: 2024, Номер 11(23)
Опубликована: Апрель 3, 2024
Abstract Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as efficient ionophore can specifically transport into mitochondria and trigger cuproptosis. However, ES be rapidly removed metabolized during intravenous administration, leading to a short half‐life limited tumor accumulation, which hampers its clinical application. Here, study develops reactive oxygen species (ROS)‐responsive polymer (PCP) based cinnamaldehyde (CA) polyethylene glycol (PEG) encapsulate ES‐Cu compound (EC), forming ECPCP. ECPCP significantly prolongs systemic circulation of EC enhances accumulation. After cellular internalization, PCP coating stimulatingly dissociates exposing high‐level ROS, releases Cu, thereby triggering via Meanwhile, 2+ ‐stimulated Fenton‐like reaction together with CA‐stimulated ROS production simultaneously breaks redox homeostasis, compensates for insufficient oxidative stress treated alone, in turn inducing immunogenic cells, achieving simultaneous cuproptosis immunotherapy. Furthermore, excessive accelerates stimuli‐dissociation ECPCP, positive feedback therapy loop against self‐alleviation. Therefore, nanoplatform immunotherapy improves dual antitumor mechanism provides potential optimization
Язык: Английский
Процитировано
42
Advanced Materials, Год журнала: 2024, Номер 36(35)
Опубликована: Июнь 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.
Язык: Английский
Процитировано
41
Advanced Science, Год журнала: 2024, Номер 11(13)
Опубликована: Янв. 25, 2024
Abstract Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy cuproptosis remains limited by poor delivery efficiency copper ion carriers. Herein, complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver into cells to induce cuproptosis. NP demonstrate stimulus‐responsive release complexes, which results mitochondrial dysfunction and promotes aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), leading Notably, not only cuproptosis, but also elicit robust immune responses suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis‐based
Язык: Английский
Процитировано
39
ACS Nano, Год журнала: 2024, Номер 18(15), С. 10495 - 10508
Опубликована: Апрель 1, 2024
Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via Jahn–Teller effect induced by introduction of Cu2+, synthesized regulated intricate microenvironment (TME) depleting endogenous glutathione (GSH) amplify oxidative stress further enhanced performance. Furthermore, cuproptosis evoked intracellular overload Cu2+ amplified SDT, leading irreversible proteotoxicity. In vitro results showed that such synergetic triggered immunogenic cell death (ICD) promoted maturation dendritic cells (DCs). as-synthesized NS-mediated thoroughly eradicated vivo solid tumors simultaneously elicited antitumor immunity suppress lung liver metastasis. Overall, this work established a nanoplatform with satisfactory immunity.
Язык: Английский
Процитировано
38
Advanced Materials, Год журнала: 2024, Номер 36(30)
Опубликована: Май 4, 2024
Abstract Low efficacy of immunotherapy due to the poor immunogenicity most tumors and their insufficient infiltration by immune cells highlights importance inducing immunogenic cell death activating system for achieving better treatment outcomes. Herein, ferroelectric Bi 2 CuO 4 nanoparticles with rich copper vacancies (named BCO‐V Cu ) are rationally designed engineered ferroelectricity‐enhanced apoptosis, cuproptosis, subsequently evoked immunotherapy. In this structure, suppressed recombination electron–hole pairs band bending polarization lead high catalytic activity, triggering reactive oxygen species bursts apoptosis. The fragments produced apoptosis serve as antigens activate T cells. Moreover, generated charge catalysis, nanomedicine can act “a smart switch” open membrane, promote nanomaterial endocytosis, shut down + outflow pathway evoke thus a strong response is triggered reduced content adenosine triphosphate. Ribonucleic acid transcription tests reveal pathways related activation. Thus, study firstly demonstrates feasible strategy enhancing using single semiconductor‐induced cuproptosis.
Язык: Английский
Процитировано
37
Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(18)
Опубликована: Фев. 23, 2024
Abstract Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task precisely conduct catalysis at tumor after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations SAzymes anticancer application are still its infancy need be developed. Herein, an situ synthesis strategy Cu was constructed convert adsorbed copper ions into isolated atoms anchored by oxygen (Cu−O 2 /Cu−O 4 ) via GSH‐responsive deformability supports. Our results suggest that activation process could further facilitate dissociation consumption glutathione, thereby leading deposition cytoplasm triggering cuproptosis. peroxidase‐like activity enabled intracellular reactive species production, resulting specifically disturbance metabolism pathway. Meanwhile, exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block glycose uptake boost cuproptosis efficacy. Overall, this effectively diminished off‐target effects SACs‐induced therapies introduced promising paradigm advancing cuproptosis‐associated therapies.
Язык: Английский
Процитировано
35
Journal of the American Chemical Society, Год журнала: 2024, Номер 146(20), С. 13805 - 13816
Опубликована: Март 29, 2024
Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity suppresses body's antitumor response. Herein, we have successfully immobilized functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing conversion H2O2 O2, thereby sensitizing Meanwhile, increased oxygenation expression hypoxia-inducible factor-1 (HIF-1) protein, resulting in alleviation immunosuppressive microenvironment. Of note, induces immunogenic (ICD), which facilitates dendritic (DC) maturation antigen presentation polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation cells complements checkpoint blockers (αPD-L1), enhancing immunity. strategy cuproptosis-mediated responses alleviating hypoxia effectively promotes activation proliferation effector T cells, ultimately leading long-term immunity against cancer.
Язык: Английский
Процитировано
35
Advanced Science, Год журнала: 2024, Номер 11(23)
Опубликована: Апрель 6, 2024
Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based
Язык: Английский
Процитировано
35