In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 11, 2024

Abstract Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, wide application GPX4 in therapy is hampered due to poor delivery efficacy and nonspecific ferroptosis. Taking advantage vivo self-assembly, we develop peptide-ferriporphyrin conjugate with microenvironment specific improve penetration, endocytosis inhibition, ultimately enhancing its anticancer activity via Briefly, inhibitory peptide conjugated an assembled linker decorated pH-sensitive moiety ferriporphyrin produce ( Gi-F-CAA ). Under acidic tumor, self-assembles into large nanoparticles (Gi-F) enhanced hydrophobic interaction after hydrolysis CAA, improving efficiency. Importantly, Gi-F exhibits substantial inhibition assembly binding AEB ) effect, augmenting oxidative stress ferriporphyrin-based Fenton reaction, enabling antitumor properties multiple models. Our findings suggest this design effect can induction ferroptosis, providing alternative overcoming chemoresistance.

Language: Английский

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Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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A bispecific glycopeptide spatiotemporally regulates tumor microenvironment for inhibiting bladder cancer recurrence

Science Advances, Journal Year: 2023, Volume and Issue: 9(9)

Published: March 1, 2023

Up to 75% of bladder cancer patients suffer from recurrence due postoperative tumor implantation. However, clinically used Bacillus Calmette-Guerin (BCG) treatment failed inhibit the recurrence. Here, we report a bispecific glycopeptide (bsGP) that simultaneously targets CD206 on tumor-associated macrophages (TAMs) and CXCR4 cells. bsGP repolarizes protumoral M2-like TAMs antitumor M1-like mediated cytotoxicity T cell recruitment. Meanwhile, is cleaved by MMP-2 enzyme form nanostructure for long-term inhibition downstream signaling, resulting in reduced metastasis promoted infiltration. In orthotopic models, rate 22%. parallel, rates 89 78% were treated doxycycline BCG clinic, respectively. Mechanistic studies reveal reduces matrix microenvironment barrier, increasing spatially redirected CD8+ cells We envision bis-targeting may pave way

Language: Английский

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Current Advances on Nanomaterials Interfering with Lactate Metabolism for Tumor Therapy

Advanced Science, Journal Year: 2023, Volume and Issue: 11(3)

Published: Nov. 8, 2023

Abstract Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount energy for fast proliferation even under oxygen‐sufficient conditions. This metabolic alteration not only favors cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition serving as byproduct glycolytic cells, plays central role the construction acidic immunosuppressive microenvironment, resulting therapeutic tolerance. Recently, targeted drug delivery inherent properties nanomaterials attracted great attention, research on modulating metabolism based enhance antitumor therapy has exploded. this review, advanced strategies interfere with are discussed, including inhibiting anabolism, promoting catabolism, disrupting “lactate shuttle”. Furthermore, recent advances combining modulation other therapies, chemotherapy, immunotherapy, photothermal therapy, reactive oxygen species‐related etc., which achieved cooperatively enhanced outcomes, summarized. Finally, foreseeable challenges prospective developments reviewed future development field.

Language: Английский

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Targeting O-GlcNAcylation in cancer therapeutic resistance: The sugar Saga continues

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216742 - 216742

Published: Feb. 23, 2024

Language: Английский

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Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 23, 2025

Language: Английский

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Canagliflozin reduces chemoresistance in hepatocellular carcinoma through PKM2-c-Myc complex-mediated glutamine starvation

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 571 - 586

Published: Sept. 9, 2023

Language: Английский

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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

National Science Review, Journal Year: 2024, Volume and Issue: 11(4)

Published: Jan. 22, 2024

ABSTRACT Mitochondriopathy inspired adenosine triphosphate (ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains prodigious challenge. Harnessing the advantages in vivo self-assembled nanomaterials, we designed an Intracellular Sequestration (IAS) system to specifically construct nanofibrous nanostructures on surface nuclei with exposed binding sites, leading highly efficient suppression bladder cancer by induction mitochondriopathy-like damages. Briefly, reported transformable nucleopeptide (NLS-FF-T) into nuclear-targeted nanoparticles sites encapsulated inside aqueous conditions. By interaction KPNA2, NLS-FF-T transformed nanofibrous-based trapper nuclei, which prevented production intracellular energy. As result, multiple cell lines (T24, EJ and RT-112) revealed that half-maximal inhibitory concentration (IC50) was reduced approximately 4-fold when compared NLS-T. Following intravenous administration, found be dose-dependently accumulated at site T24 xenograft mice. More significantly, this IAS exhibited extremely antitumor efficacy according deterioration tumors simultaneously prolonged overall survival orthotopic Together, our findings clearly demonstrated therapeutic sequestration-induced damages, provides potential treatment strategy malignancies.

Language: Английский

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An In Vivo Self‐Assembled Bispecific Nanoblocker for Enhancing Tumor Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(45)

Published: July 18, 2023

Anti-PD-L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T-cells activation. However, the excessive accumulation of extracellular matrix components induced unsatisfactory infiltration and poor penetration antibodies make it challenging to realize efficient immunotherapy. Herein, a peptide-based bispecific nanoblocker (BNB) strategy is reported for situ construction CXCR4/PD-L1 targeted nanoclusters on surface cells that are capable boosting through CXCR4 blockage enhancing activation PD-L1 occupancy, ultimately realizing high-performance Briefly, BNB selectively recognizes bonds with deep penetration, which rapidly self-assembles into cells. Compared traditional antibody, exhibits an intriguing metabolic behavior, is, elimination half-life (t1/2 ) 69.3 h ≈50 times longer than plasma (1.4 h). The higher rapid systemic clearance overcome potential side effects. Moreover, solid stress generated substantially reduced 44%, promotes efficacy. Finally, these findings strengthen extend clinical applications PD-1/PD-L1

Language: Английский

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Applications of nanofibers drug delivery system in cancer therapy

Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 90, P. 105128 - 105128

Published: Nov. 2, 2023

Language: Английский

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