Biodegradable copper-doped calcium phosphate nanoplatform enables tumor microenvironment modulations for amplified ferroptosis in cervical carcinoma treatment DOI Creative Commons

Guangji Yang,

Dongyan Ren,

Tao Yu

et al.

International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 9, P. 100315 - 100315

Published: Dec. 17, 2024

As a recently discovered form of regulated cell death, ferroptosis has attracted much attention in the field cancer therapy. However, achieving considerably enhanced efficacy is often restricted by overexpression endogenous glutathione (GSH) tumor microenvironment (TME). In this work, we report ferroptosis-inducing strategy GSH depletion and reactive oxygen species (ROS) generation based on biodegradable copper-doped calcium phosphate (CaP) with L-buthionine sulfoximine (BSO) loading (denoted as BSO@CuCaP-LOD, BCCL). BCCL was conducted biomineralization approach using lactate oxidases (LOD) bio-template to obtain Cu-doped CaP nanoparticles. Then, BSO loaded nanoparticles pH-responsive biodegradability endow controlled release Cu2+ response acidic TME. Benefiting from catalytic performance LOD, efficiently depletes level tumor, which can generate H2O2 for subsequent Fenton-like reaction. The intracellular followed GSH-mediated Cu2+/Cu+ conversion, leading inhibition peroxidase 4 (GPX4) •OH radicals via Cu+-mediated confers induction LOD-induced production, BSO-mediated depletion, ROS generation, cause effective ferroptotic damage. verified vitro vivo assays, designed nanoplatform highly biocompatible exhibits superior anticancer therapy uterine cervical carcinoma U14 xenografts. This study, therefore, provides therapeutic platform that modulating TME enable intensive generating depleting performance, well an innovative paradigm ferroptosis-based

Language: Английский

New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy DOI Creative Commons

Yibin Lin,

Yifu Song, Yaochuan Zhang

et al.

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

Published: March 17, 2025

Abstract Recent breakthroughs in tumor immunotherapy have confirmed the capacity of immune system to fight several cancers. The effective means treating cancer involves accelerating death cells and improving patient immunity. Dynamic changes microenvironment alter actual effects anti-tumor drug production may trigger favorable or unfavorable responses by modulating tumor-infiltrating lymphocytes. Notably, CD8 + T are one primary that provide response. Tumor stem will resist evade destruction through various mechanisms as exert their function. This paper reviews research on regulation development prognosis directly indirectly role cells. We also discuss related strategies.

Language: Английский

Citations

3
Structure, function, signaling pathways and clinical therapeutics: The translational potential of STAT3 as a target for cancer therapy DOI
Dandan Shi,

Jiejing Tao,

Shuli Man

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189207 - 189207

Published: Nov. 1, 2024

Language: Английский

Citations

7
Ferroptosis as a new tool for tumor suppression through lipid peroxidation DOI Creative Commons
Xin Yang, Yanqing Liu, Zhe Wang

et al.

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

Published: Nov. 9, 2024

As a newly defined type of programmed cell death, ferroptosis is considered potent weapon against tumors due to its distinct mechanism from other types death. Ferroptosis triggered by the uncontrolled accumulation hydroperoxyl polyunsaturated fatty acid-containing phospholipids, also called lipid peroxidation. The peroxidation, generated through enzymatic and non-enzymatic mechanisms, drives changes in morphology destruction membrane integrity. Here, we dissect mechanisms induced enzymatically or non-enzymatically, summarize major metabolism pathways modulating provide insights into relationship between tumor suppression. In this review, discuss recent advances microenvironments prospect potential therapeutic application.

Language: Английский

Citations

4
Simple and Smart Metal–Phenolic Micelles for Optimizing Immunotherapy by Disrupting Tumor Stemness DOI
Yaping Wang, Xin Wang, Yuping He

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

cGAS-STING pathway activation has attracted considerable attention in antitumor immunotherapy, but clinical outcomes lag behind expectations due to overlooked negative feedback mechanisms. Here, we determine that STING promotes tumor stemness, which weakens the efficacy of STING-based therapies, presenting a double-edged sword. To address this therapeutic paradox, simple metal-phenolic polymeric micelle (HMQ) was developed, Mn2+ (a agonist) is coordinated with quercetin stemness inhibitor) and hyaluronic acid (HA), unlock full potential pathway. This unique coordination structure integrates active targeting rapid pH-responsive drug release. Importantly, released drugs remained their original form, avoiding changes bioactivity. HMQ effectively mitigates stemness-promoting effects activation, thus significantly amplifying potency cGAS-STING-based therapies. intelligent facile establishes new generation agonists promising translatability provides flexible platform for win–win strategy.

Language: Английский

Citations

0
Core–Shell Nanoparticles with Sequential Drug Release Depleting Cholesterol for Reverse Tumor Multidrug Resistance DOI

Jieke Zhang,

Yingying Zhou,

Jialing Guo

et al.

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

Published: Jan. 15, 2025

Multidrug resistance (MDR) facilitates tumor recurrence and metastasis, which has become a main cause of chemotherapy failure in clinical. However, the current therapeutic effects against MDR remain unsatisfactory, mainly hampered by rigid structure drug-resistant cell membranes uncontrolled drug release. In this study, based on sequential release strategy, we engineered core–shell nanoparticle (DOX-M@CaP@ATV@HA) depleting cholesterol for reverse MDR. DOX-M@CaP@ATV@HA could accurately target cells due to active targetability hyaluronic acid (HA) toward CD44 receptors. The calcium phosphate (CaP) shell was cleaved lysosomal acidic environment so that cholesterol-lowering atorvastatin (ATV) rapidly released diminish P-glycoprotein (P-gp) level membrane, thereby boosting uptake. Next, doxorubicin (DOX) gradually from hydrophobic core mPEG-DSPE micelle, inflicting irreversible DNA damage triggering apoptosis. nanosystem proven both vitro vivo effectively exhibited remarkable efficacy tumors with high biosafety. conclusion, reverses via depletion, provides an innovative strategy treatment.

Language: Английский

Citations

0
Biomedical engineering targeting cancer stem cells to reinforce cancer therapy DOI

Shumin Sun,

Nailin Yang, Zifan Pei

et al.

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 530, P. 216494 - 216494

Published: Feb. 4, 2025

Language: Английский

Citations

0
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions DOI
Xiaoyu Cui, Bin Chen, Ying Chen

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Emerging evidence indicates that modulating glutathione peroxidase 4 (GPX4) to induce ferroptosis is a promising strategy for tumor treatment. However, most of the GPX4 small molecule inhibitors face limitations due their poor delivery efficacy and low specificity activation. Herein, ferroptosis‐inducing nanomedicine developed integrates nutlin‐3 with iridium oxide nanoclusters (NUT‐IrO x NCs) enhanced ferroptosis‐driven multimodal therapeutic in colorectal cancer (CRC). This NUT‐IrO NCs can (GSH) depletion via Ir (VI)‐Ir (III) transition, while nutlin‐3, well‐established inhibitor p53‐MDM2 interaction, suppresses GSH production by modulation p53/SLC7A11/xCT signaling pathway. The reduction intracellular results pronounced reductions enzymatic activity, consequently leading lipid peroxidation accumulation further enhancing ferroptosis‐induced CRC therapy. dual‐pronged approach demonstrates robust anticancer effects favorable biocompatibility both vitro vivo models. study provides an effective highlights benefits inhibiting GSH/GPX4 activating multiple regulatory pathways, providing alternative avenue

Language: Английский

Citations

0
Therapeutic and prognostic values of ferroptosis signature in glioblastoma DOI
Reza Nedaeinia, Hassan Dianat‐Moghadam,

Maedeh Movahednasab

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114597 - 114597

Published: April 15, 2025

Language: Английский

Citations

0
Mannose modified graphene oxide drug-delivery system targets cancer stem cells and tumor-associated macrophages to promote immunotherapeutic efficacy DOI
Jiapu Wang, Ziwei Liang, Yuhui Wang

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 253, P. 114710 - 114710

Published: April 17, 2025

Language: Английский

Citations

0
Radiation-triggerable bioreactors enable bioenergetic reprograming of cancer stem cell plasticity via targeted arginine metabolism disruption for augmented radio-immunotherapy DOI
Xuemei Yao, Huocheng Yang, Sanxing Guo

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 322, P. 123391 - 123391

Published: May 5, 2025

Language: Английский

Citations

0