A Mitochondrion‐Targeted NIR‐II Modulator for Synergistic Ferroptosis–Immunotherapy DOI
Miao Wang, Qihang Ding, Wuyue Su

et al.

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

Published: April 14, 2025

Abstract Immune checkpoint inhibitors (ICIs) have limited clinical efficacy against gastric cancer (GC) due to the nonimmunogenic tumor microenvironment. Therefore, inducing immunogenic cell death (ICD) reprogram landscape is essential. This study develops HD‐FA nanoparticles by encapsulating a novel mitochondrion‐targeted NIR‐II modulator, HD, within DSPE‐PEG‐FA. exhibits superior spatiotemporal resolution, robust accumulation, and minimal adverse effects. Upon 808 nm laser irradiation, generates reactive oxygen species, leading ferroptosis oxidative stress damage in GC cells inhibiting SLC7A11/GSH/GPX4 axis. triggers ICD, resulting antitumor activity not only primary tumors but also distant tumors. Moreover, promotes dendritic maturation, increases effector‐memory T‐cell frequency, reduces presence of myeloid‐derived suppressor cells, thereby fostering enhanced immunity. presents first report modulator for synergistic therapy with ICIs, marking significant advancements fight GC.

Language: Английский

Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 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.

Language: Английский

Citations

90
Complex roles of autophagy in cancer development, immune evasion, and drug resistance DOI

Xuegang Niu,

Qi Sheng You, Kejun Hou

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 78, P. 101170 - 101170

Published: Nov. 15, 2024

Language: Английский

Citations

24
Cuproptosis: unveiling a new frontier in cancer biology and therapeutics DOI Creative Commons

Ying Feng,

Zhibo Yang, Jianpeng Wang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 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.

Language: Английский

Citations

22
Dual-Responsive Nanomedicine Activates Programmed Antitumor Immunity through Targeting Lymphatic System DOI
Hong Xiao, Xiaoxia Li, Simin Liang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(17), P. 11070 - 11083

Published: April 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.

Language: Английский

Citations

20
Celecoxib Augments Paclitaxel-Induced Immunogenic Cell Death in Triple-Negative Breast Cancer DOI
Xiaohui Qian, Yang Huang, Ziqiang Ye

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(24), P. 15864 - 15877

Published: June 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

Language: Английский

Citations

14
A Self‐Cascading Catalytic Therapy and Antigen Capture Scaffold‐Mediated T Cells Augments for Postoperative Brain Immunotherapy DOI

Bhanu Nirosha Yalamandala,

Thrinayan Moorthy, Zhuo‐Hao Liu

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, phenomenon immune privilege and generally low immunogenicity vaccines often reduce presence within brain tumors, especially in tumor clusters. In this study, an implantable self‐cascading catalytic therapy antigen capture scaffold (CAS) that can boost efficiency at post‐surgery antigens via urethane‐polyethylene glycol‐polypropylene glycol (PU‐EO‐PO) segments are developed postoperative CAS consists 3D‐printed elastomers modified iron (Fe 2+ ) metal‐organic frameworks (MOFs, MIL88) acts as a programmed peroxide mimic cancer cells to initiate Fenton reaction sustain ROS production. With assistance chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts self‐defense mechanism, further enhances cytotoxicity, releases antigens. Then, containing PU‐EO‐PO groups depot detain autologous tumor‐associated dendritic maturation cell augments sustained stimulation. enhanced response tumors improved survival

Language: Английский

Citations

12
Nanoplatform-based strategies for enhancing the lethality of current antitumor PDT DOI

Xinxin Lu,

Chun Xue,

Jianhui Dong

et al.

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(13), P. 3209 - 3225

Published: Jan. 1, 2024

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

Language: Английский

Citations

10
Nanotherapeutics targeting autophagy regulation for improved cancer therapy DOI Creative Commons
Yunmeng Liu, Yaxin Wang, Jincheng Zhang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(6), P. 2447 - 2474

Published: March 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.

Language: Английский

Citations

10
Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy DOI Creative Commons
Zdeněk Kejík, Jan Hajduch, Nikita Abramenko

et al.

Communications Chemistry, Journal Year: 2024, Volume and Issue: 7(1)

Published: Aug. 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.

Language: Английский

Citations

10
Ultrasound-Responsive Nanobubbles for Breast Cancer: Synergistic Sonodynamic, Chemotherapy, and Immune Activation through the cGAS-STING Pathway DOI

Huan Pu,

Jia Huang,

Bin Gui

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

2