Dual Strategy of Ca2+ Influx and Collagen Denaturation to Remodel the Extracellular Matrix and Amplify Sonopiezoelectric Therapy DOI
Chenghao Yu, Desheng Chen, Dingcheng Zhu

et al.

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

Published: May 30, 2025

Abstract Extracellular matrix (ECM), a core member of tumor microenvironment, is ≈1.5‐fold harder than the surrounding normal tissues. Regulating stiffness ECM can significantly impact physiological activities cells, such as growth, differentiation, and migration. Herein, sonopiezoelectric‐response nanoplatform consisting Cu 3 BiS nanospheres (CBS NSs) constructed for remodeling. Sonopiezoelectric therapy (SPT) chemodynamic (CDT) are conducted using ultrasound (US) near‐infrared irradiation. Under US irradiation, mechanical strain CBS NSs causes piezoelectric polarization promotes redox reaction through energy band bending. The built‐in electric field generated by irradiation amplifies efficiency Fenton‐like substantially enhances reactive oxygen species production. Moreover, property‐mediated electrical signals allow Ca 2+ influx, upregulating levels metalloproteinase (MMP)‐2 MMP‐9. Integrating with generates localized heat, which effectively denature collagen, reduce stiffness, enhance permeability into solid tumors, thus improving SPT effect. combination MMP upregulation collagen degradation maximize benefits remodeling synergistically cancer therapeutic efficacy SPT/CDT. This SPT/CDT synergistic platform an innovative strategy therapy.

Language: Английский

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer DOI Creative Commons
Shan Liu,

Xingda Zhang,

Wenzheng Wang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 21, 2024

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth contributes treatment resistance. In primary breast metabolic shifts such as the Warburg effect enhanced lipid synthesis are closely linked chemotherapy failure. Similarly, metastatic lesions often display distinct profiles that not only sustain but also confer resistance targeted therapies immunotherapies. The review emphasizes two major aspects: mechanisms driving in both how unique environments sites further complicate treatment. By targeting vulnerabilities at stages, new strategies could improve efficacy existing provide better outcomes for cancer patients.

Language: Английский

Citations

20
GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer DOI Creative Commons
Mingxing Xie, Hao Qin, Liu Li

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 19, 2025

Abstract Background Brain metastasis (BrM) poses a significant challenge to the prognosis and quality of life for patients with non-small cell lung cancer (NSCLC). Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system (CNS), has been implicated progression various tumors. However, its potential role BrM NSCLC underlying mechanisms remain largely unexplored. Methods A multi-omics approach combined vivo vitro experiments identified GABA as key target NSCLC. Functional mechanistic studies were conducted investigate how mediates brain through activation NF-κB pathway. Results levels significantly elevated both cells serum who had BrM. markedly enhanced metastatic capabilities malignancy cells. Mechanistically, tumor tendency can inhibit 4-aminobutyrate aminotransferase (ABAT) by downregulating forkhead box A2 (FOXA2) expression, leading increased accumulation. subsequently activates pathway astrocytes, thus facilitating Conclusions Our findings indicate that plays crucial development activating FOXA2/ABAT/GABA axis. Additionally, interaction between astrocytes creates microenvironment promotes colonization.

Language: Английский

Citations

6
PD-L1-Targeting Autophagy Modulator to Upregulate MHC-I and Activate Photo-Immunotherapy for Metastatic Tumor Eradication DOI
Zhen‐Ming Lu,

Ziwen Qiu,

Yanmei Li

et al.

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

Published: March 25, 2025

Breast cancer cells are characterized by heightened autophagy, which impairs tumor-associated antigen presentation and represents a significant barrier to the antitumor immunity. In this study, PD-L1-targeting autophagy modulator (PFC@CQ) is fabricated activate photoimmunotherapy against breast cancer. Specifically, hydrophobic photosensitizer protoporphyrin IX (PpIX) covalently linked peptide FFVLK sequence CLQKTPKQC, resulting in formation of an amphiphilic photosensitizer-peptide conjugate (PpIX-FFVLK-CLQKTPKQC, called PFC), capable encapsulating inhibitor chloroquine (CQ). PFC@CQ can not only facilitate targeted drug codelivery PD-L1-overexpressing cells, but also effectively disrupt their immune evasion blocking PD-1/PD-L1 pathway. Upon light irradiation, photodynamic therapy (PDT) induces tumor cell destruction immunogenic death (ICD), causing release damage-associated molecular patterns (DAMPs). Simultaneously, inhibit pathway mediate upregulation MHC-I, thereby enhancing presentation. This cascade immunomodulation promotes dendritic maturation CD8+ T activation, leading synergistic suppression both primary metastatic tumors. work introduces innovative modulation strategy with potent immunomodulatory capability, demonstrating potential trigger systemic responses through local treatment.

Language: Английский

Citations

3
Silver niobate/platinum piezoelectric heterojunction enhancing intra-tumoral infiltration of immune cells for transforming “cold tumor” into “hot tumor” DOI
Jinhui Zhang, Zhong‐Yi Dong, Chunlei Xue

et al.

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 690, P. 137303 - 137303

Published: March 12, 2025

Language: Английский

Citations

2
Self‐Oxygenated Hydrogel Enhances Immune Cell Response and Infiltration Via Triggering Dual DNA Damage to Activate cGAS‐STING and Inhibiting CAFs DOI
Huiting Tian, Nan Zhu, Haiting Wang

et al.

Small, Journal Year: 2024, Volume and Issue: 20(45)

Published: July 25, 2024

Abstract Immune checkpoint inhibitors (ICIs) offer promise in breaking through the treatment and survival dilemma of triple‐negative breast cancer (TNBC), yet only immunomodulatory subtype ≈5% TNBC patients respond as monotherapy due to lack effector immune cells (internal problem) physical barrier (external limitation) formed by cancer‐associated fibroblasts (CAFs). A hydrogel drug‐delivery platform, ALG@TBP‐2/Pt(0)/nintedanib (ALG@TPN), is designed induce strong functions dual elimination internal external tumor microenvironment (TME). Activated white light, type I II photodynamic therapy (PDT), TBP‐2 generates large amounts reactive oxygen species (ROS) intracellularly, oxidizing mitochondrial DNA (mtDNA). The unique catalase activity Pt(0) converts endogenous H 2 O , reducing anoxia‐limiting PDT enhancing ROS generation efficacy. Abundant can oxidize cytotoxic Pt(II), damaging nuclear (nDNA). Dual damage mtDNA nDNA might bi‐directionally activate cGAS/STING pathway enhance cell response. Besides, nintedanib demonstrates a significant inhibitory effect on CAFs, weakening deepening infiltration. Overall, study provides self‐oxygenating with “PDT/chemotherapy/anti‐CAFs” effect, triggering reshape TME. Both interventions increase anti‐TNBC responses.

Language: Английский

Citations

8
Remodeling tumor microenvironment by versatile nanoplatform orchestrated mechanotherapy with chemoimmunotherapy to synergistically enhance anticancer efficiency DOI
Wenqiang Chen, Zhe Zhang, Yunfei Han

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123104 - 123104

Published: Jan. 10, 2025

Language: Английский

Citations

1
Plasma Membrane Targeted Photodynamic Nanoagonist to Potentiate Immune Checkpoint Blockade Therapy by Initiating Tumor Cell Pyroptosis and Depleting Infiltrating B Cells DOI
Yingtao Zhong,

Ziwen Qiu,

Keyan Zhang

et al.

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

Published: Feb. 26, 2025

Abstract Immune checkpoint blockade (ICB) therapy has achieved remarkable benefits in the treatment of malignant tumors, but clinical response rates are unsatisfied due to low tumor immunogenicity and abundant immunosuppressive cells. Herein, a plasma membrane targeted photodynamic nanoagonist (designated as PMTPN) is developed potentiate ICB by initiating cell pyroptosis depleting infiltrating B PMTPN composed rationally designed chimeric peptide sequence loaded with Bruton's tyrosine kinase inhibitor (Ibrutinib). Notably, capable sequentially targeting trigger immunogenic cause overwhelming release cytokines, promoting dendritic cells maturation, cytotoxic T lymphocytes (CTLs) activation. Meanwhile, can also deplete reduce secretion interleukin‐10 decrease regulatory enhance CTLs infiltration. Beneficially, synergistic immune modulating characteristics simultaneously eliminate primary distant tumors. This study offers promising strategy elevate immunotherapeutic rate consideration complex factors.

Language: Английский

Citations

1
Stimuli-responsive polymer-dasatinib prodrug to reprogram cancer-associated fibroblasts for boosted immunotherapy DOI
Yuxin Zhang, Jie Zhou, Yiyan Wang

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 381, P. 113606 - 113606

Published: March 5, 2025

Language: Английский

Citations

1
Advances in nanotechnology for targeting cancer-associated fibroblasts: A review of multi-strategy drug delivery and preclinical insights DOI Creative Commons

Zhongsong Zhang,

Yujie Tang,

Dan Luo

et al.

APL Bioengineering, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 1, 2025

Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment by promoting growth, immune evasion, and metastasis. Recently, drug delivery systems targeting CAFs have emerged as promising long-term effective approach to cancer treatment. Advances nanotechnology, particular, led development of nanomedicine designed specifically target CAFs, offering new possibilities for precise personalized therapies. This article reviews recent progress using nanocarriers that CAFs. Additionally, we explore potential combining multiple therapies, such chemotherapy immunotherapy, with enhance efficacy overcome resistance. Although many preclinical studies show promise, clinical application still faces considerable challenges, especially terms penetration large-scale production. Therefore, this review aims provide fresh perspective on CAF-targeted highlight future research directions applications.

Language: Английский

Citations

1
The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics DOI Creative Commons
Jian Tang, Yu Chen,

Chunhua Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 28, 2024

Abstract Mesenchymal stem cells (MSCs) are recruited by malignant tumor to the microenvironment (TME) and play a crucial role in initiation progression of tumors. This encompasses immune evasion, promotion angiogenesis, stimulation cancer cell proliferation, correlation with cells, multilineage differentiation within TME, development treatment resistance. Simultaneously, extensive research is exploring homing effect MSCs MSC‐derived extracellular vesicles (MSCs‐EVs) tumors, aiming design them as carriers for antitumor substances. These substances targeted deliver drugs enhance drug efficacy while reducing toxicity. paper provides review supportive associated molecular mechanisms. Additionally, we summarize latest therapeutic strategies involving engineered MSCs‐EVs treatment, including their utilization gene agents, chemotherapeutics, oncolytic viruses. We also discuss distribution clearance upon entry into body elucidate potential therapies based on along challenges they face.

Language: Английский

Citations

4