Cuproptosis: Harnessing Transition Metal for Cancer Therapy

ACS Nano, Год журнала: 2023, Номер 17(20), С. 19581 - 19599

Опубликована: Окт. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Язык: Английский

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Complex roles of autophagy in cancer development, immune evasion, and drug resistance

Drug Resistance Updates, Год журнала: 2024, Номер 78, С. 101170 - 101170

Опубликована: Ноя. 15, 2024

Язык: Английский

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Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

Язык: Английский

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Dual-Responsive Nanomedicine Activates Programmed Antitumor Immunity through Targeting Lymphatic System

ACS Nano, Год журнала: 2024, Номер 18(17), С. 11070 - 11083

Опубликована: Апрель 19, 2024

Effective antitumor immunotherapy depends on evoking a cascade of cancer-immune cycles with lymph nodes (LNs) as the initial sites for activating immunity, making drug administration through lymphatic system highly attractive. Here, we describe nanomedicine dual responsiveness to pH and enzyme programmed activation immune system. The proposed can release STING agonist diABZI-C2-NH2 in LNs' acidic environment activate dendritic cells (DCs) T cells. Then, remaining hitchhikes activated (PD-1+ cells) binding PD-1, resulting an effective delivery into tumor tissues owing tumor-homing capacity PD-1+ matrix metalloproteinase-2 (MMP-2) being enriched tissue triggers PD-1 antibody (aPD-1) which exerts checkpoint blockade (ICB) therapy. Eventually, delivers DNA methylation inhibitor GSK-3484862 (GSK) cells, then latter combines granzyme B (GZMB) trigger cell pyroptosis. Consequently, pyroptotic induce robust immunogenic death (ICD) enhancing DCs maturation initiating cascading response. Study 4T1 breast mouse model demonstrates prominent therapeutic outcome this creating positive feedback loop cancer-immunity including LNs, cell-mediated delivery, ICB therapy, pyroptosis-featured ICD.

Язык: Английский

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Celecoxib Augments Paclitaxel-Induced Immunogenic Cell Death in Triple-Negative Breast Cancer

ACS Nano, Год журнала: 2024, Номер 18(24), С. 15864 - 15877

Опубликована: Июнь 3, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks effective targeted therapies. Inducing immunogenic cell death (ICD) in tumor cells represents promising strategy to enhance therapeutic efficacy by promoting antitumor immunity. Paclitaxel (PTX), commonly used chemotherapy drug for TNBC, can induce ICD; however, the resulting immunogenicity limited. Thus, there an urgent need explore strategies improve effectiveness of ICD TNBC incorporating immunoregulatory agents. This study investigated potential celecoxib (CXB) PTX-induced blocking biosynthesis PGE2 cells. We observed combination CXB and PTX promoted maturation dendritic primed T cell-dependent immune response, leading enhanced rejection vaccination assay. To further optimize delivery vivo, we developed cRGD-modified liposomes codelivery PTX. system significantly improved accumulation triggered robust immunity orthotopic mouse model TNBC. Moreover, it served as situ vaccine inhibit recurrence lung metastasis. Overall, our findings provide in-depth insights into mechanism underlying PTX, highlighting their immune-based therapies

Язык: Английский

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Nanoplatform-based strategies for enhancing the lethality of current antitumor PDT

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(13), С. 3209 - 3225

Опубликована: Янв. 1, 2024

This review summarizes the recent advances of nanoplatform-based strategies to efficiently amplify tumoricidal capability PDT.

Язык: Английский

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Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Авг. 13, 2024

Abstract Mitochondrial dysregulation plays a significant role in the carcinogenesis. On other hand, its destabilization strongly represses viability and metastatic potential of cancer cells. Photodynamic photothermal therapies (PDT PTT) target mitochondria effectively, providing innovative non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show enhancing PDT PTT. The limitations cyanine dyes for PTT are discussed, along their applications combination therapies, theranostic techniques, optimal delivery systems. Additionally, novel approaches sonodynamic therapy using photoactive presented, highlighting advances treatment.

Язык: Английский

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Ultrasound-Responsive Nanobubbles for Breast Cancer: Synergistic Sonodynamic, Chemotherapy, and Immune Activation through the cGAS-STING Pathway

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Breast cancer remains the leading cause of cancer-related deaths among women worldwide, necessitating more effective treatment strategies. Chemotherapy combined with immunotherapy is first-line for breast cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to poor delivery efficiency, drug resistance tumor cells, immunosuppressive microenvironment. This study explores development ultrasound-responsive nanobubbles (Ce6/PTX Nbs) targeted imaging sonoimmunotherapy in treatment. By integrating sonodynamic therapy (SDT), chemotherapy, immunotherapy, aim address challenges such as delivery, systemic toxicity, immune suppression conventional therapies. The nanobubbles, composed sonosensitizer chlorin e6 (Ce6)-modified phospholipid loaded chemotherapeutic agent paclitaxel (PTX) enhancing drug-loading capacity, designed precisely target sites via cyclic-RGD peptides. Upon ultrasound activation, Ce6 induces reactive oxygen species (ROS), promoting immunogenic cell death (ICD), while PTX disrupts mitosis, response. nanobubbles' responsiveness facilitates real-time controlled release, maximizing efficacy minimizing effects. Key findings demonstrate that Ce6/PTX Nbs significantly reduced growth a 4T1 model, enhanced activation cGAS-STING pathway, increased infiltration CD8+ T cells both primary distant tumors. In combination anti-PD-L1 checkpoint inhibitors, achieved substantial metastasis. innovative approach offers highly targeted, effective, minimally toxic potential clinical translation its dual capabilities.

Язык: Английский

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Laser‐Ignited Lipid Peroxidation Nanoamplifiers for Strengthening Tumor Photodynamic Therapy Through Aggravating Ferroptotic Propagation and Sustainable High Immunogenicity

Small, Год журнала: 2023, Номер 20(14)

Опубликована: Ноя. 22, 2023

Abstract Photodynamic therapy (PDT) is extensively investigated for tumor in the clinic. However, efficacy of PDT severely limited by tissue penetrability light, short effective half‐life and radius reactive oxygen species (ROS), weak immunostimulatory effect. In this study, a glutathione (GSH)‐activatable nano‐photosensitizer developed to load with arachidonic acid (AA) camouflage erythrocyte membrane, which serves as laser‐ignited lipid peroxidation nanoamplifier (MAR). The photosensitive effect MAR recovered accompanied degradation microenvironment triggers AA upon laser excitation. Interestingly, it aggravates propagation ferroptosis among cancer cells driving continuous chain reactions participation products, ferrous ions (Fe 2+ ), AA. Consequently, even deep‐seated without illumination also undergo owing ferroptotic signal. Moreover, residual undergoing still maintain high immunogenicity after PDT, thus continuously triggering sufficient tumor‐associated antigens (TAAs) release remarkably promote anti‐tumor immune response. Therefore, study will provide novel “all‐in‐one” that not only amplifies damaging expands range but improves PDT.

Язык: Английский

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Nanotherapeutics targeting autophagy regulation for improved cancer therapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(6), С. 2447 - 2474

Опубликована: Март 18, 2024

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development nanomedicine, nanomaterials have been widely utilized in therapy due their unrivaled delivery performance. Hence, considering potential benefits integrating autophagy nanotechnology therapy, we outline latest advances autophagy-based nanotherapeutics. Based on brief background related nanotherapeutics impact tumor progression, feasibility treatment demonstrated. Further, developed modulate are reviewed from perspective cell signaling pathways, including modulation mammalian rapamycin (mTOR) pathway, autophagy-related (ATG) its complex expression, reactive oxygen species (ROS) mitophagy, interference autophagosome-lysosome fusion, inhibition hypoxia-mediated autophagy. In addition, combination which nano-autophagy combined chemotherapy, phototherapy, immunotherapy also described. Finally, prospects challenges efficient envisioned.

Язык: Английский

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