A Self‐Assembled 3D Model Demonstrates How Stiffness Educates Tumor Cell Phenotypes and Therapy Resistance in Pancreatic Cancer

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(17)

Published: March 12, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression therapy resistance. To further the understanding of how stiffening microenvironment (TME) contributes to aggressiveness, three‐dimensional (3D) self‐assembling hydrogel disease model developed based on peptide amphiphiles (PAs, PA‐E3Y ) designed tailor stiffness. The displays nanofibrous architectures reminiscent native TME enables study invasive behavior PDAC cells. Enhanced tuneability stiffness demonstrated interacting thermally annealed aqueous solutions (PA‐E3Y h divalent cations create hydrogels mechanical properties ultrastructure similar ECM. It shown that levels found in induces ECM deposition, promotes epithelial‐to‐mesenchymal transition (EMT), enriches CD133 + /CXCR4 cancer stem cells (CSCs), subsequently enhances drug findings reveal 3D environment renders more aggressive therefore faithfully recapitulates vivo tumors.

Language: Английский

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Recent Advances in Nanomaterials for Modulation of Stem Cell Differentiation and Its Therapeutic Applications

Biosensors, Journal Year: 2024, Volume and Issue: 14(8), P. 407 - 407

Published: Aug. 22, 2024

Challenges in directed differentiation and survival limit the clinical use of stem cells despite their promising therapeutic potential regenerative medicine. Nanotechnology has emerged as a powerful tool to address these challenges enable precise control over cell fate. In particular, nanomaterials can mimic an extracellular matrix provide specific cues guide proliferation field nanotechnology. For instance, recent studies have demonstrated that nanostructured surfaces scaffolds enhance lineage commitment modulated by intracellular regulation external stimulation, such reactive oxygen species (ROS) scavenging, autophagy, or electrical stimulation. Furthermore, nanoframework-based upconversion nanoparticles be used deliver bioactive molecules, growth factors, genetic materials facilitate tissue regeneration. The increasing nanostructures research led development new approaches. Therefore, this review provides overview advances for modulating differentiation, including metal-, carbon-, peptide-based strategies. addition, we highlight nano-enabled technologies applications therapy focusing on improving efficiency therapeutics. We believe will inspire researchers intensify efforts deepen understanding, thereby accelerating modulation, pharmaceutical industry,

Language: Английский

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Unraveling the Role of the Tumor Extracellular Matrix to Inform Nanoparticle Design for Nanomedicine

Advanced Science, Journal Year: 2024, Volume and Issue: 12(2)

Published: Dec. 4, 2024

Abstract The extracellular matrix (ECM)—and its mechanobiology—regulates key cellular functions that drive tumor growth and development. Accordingly, mechanotherapy is emerging as an effective approach to treat fibrotic diseases such cancer. Through restoring the ECM healthy‐like conditions, this treatment aims improve tissue perfusion, facilitating delivery of chemotherapies. In particular, manipulation gaining interest a valuable strategy for developing innovative treatments based on nanoparticles (NPs). However, further progress required; instance, it known presence dense ECM, which hampers penetration NPs, primarily impacts efficacy nanomedicines. Furthermore, most 2D in vitro studies fail recapitulate physiological deposition components. To address these issues, comprehensive understanding interactions between NPs needed. This review focuses main features complex interplay with NPs. Recent advances are discussed insights offered into how combination nanomedicine can help nanomaterials design advance their clinical translation.

Language: Английский

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Extracellular matrix in cancer progression and therapy

Medical Review, Journal Year: 2022, Volume and Issue: 2(2), P. 125 - 139

Published: April 1, 2022

Abstract The tumor ecosystem with heterogeneous cellular compositions and the microenvironment has increasingly become focus of cancer research in recent years. extracellular matrix (ECM), major component microenvironment, its interactions cells stromal have also enjoyed tremendously increased attention. Like other components ECM solid tumors differs significantly from that normal organs tissues. We review studies complex roles plays progression, initiation, growth to angiogenesis invasion. highlight biomolecular, biophysical, mechanochemical between not only regulate steps but affect efficacy systemic treatment. further discuss strategies target modify improve therapy.

Language: Английский

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Dynamic links between mechanical forces and metabolism shape the tumor milieu

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 84, P. 102218 - 102218

Published: Aug. 17, 2023

Cell function relies on the spatiotemporal dynamics of metabolic reactions. In all physiopathological processes tissues, mechanical forces impact structure and membranes, enzymes, organelles regulators gene programs, thus regulating cell metabolism. turn, pathways feedback impacts physical properties tissues. Hence, metabolism tissue mechanics are dynamically intertwined continuously interact. Cancer is akin to an ecosystem, comprising tumor cells various subpopulations stromal embedded in altered extracellular matrix. The progression cancer, from initiation advanced stage metastasis, driven by genetic mutations crucially influenced alterations microenvironment. These also play a pivotal role cancer evasion immune surveillance developing resistance treatments. Here, we highlight emerging evidence showing that mechano-metabolic circuits regulate multiple crucial for discuss potential approaches improve therapeutic treatments interfering with these circuits.

Language: Английский

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