Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics DOI Creative Commons
Stephanie R. Jackson, Joseph P. Flemming,

Kübra Karagoz

et al.

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(11)

Published: Oct. 30, 2024

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue achieve or seek approval, setbacks are often attributed a lack efficacy, failure clinical endpoints, dose-limiting toxicities. Successful efforts have characterized by the development therapeutics designed specifically deliver optimal dosing tumour cells while minimizing off-target toxicity. Much effort devoted rational design application synthetic nanoparticles serve as targeted therapeutic delivery vehicles. Several challenges successful this modality vehicles include induction protracted immune response that results in their rapid systemic clearance, manufacturing cost, stability, biocompatibility. Extracellular vesicles (EVs) heterogeneous class endogenous biologically produced lipid bilayer mediate intercellular communication carrying bioactive macromolecules capable modifying cellular phenotypes local distant cells. By genetic, chemical, metabolic methods, extracellular can be engineered display targeting moieties on surface transporting specific cargo modulate pathological processes following uptake target cell populations. This review will survey types EVs, composition cargoes, strategies employed increase targeting, uptake, release, potential

Language: Английский

Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites DOI Creative Commons
Yun Teng, Chao Luo,

Xiaolan Qiu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Abstract Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate plant-derived nanoparticles (PNP) on and metabolites in context cancer immunotherapy with humanized gnotobiotic mouse model. Specifically, show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae Lactobacillaceae mediated digalactosyldiacylglycerol (DGDG) glycine, respectively. We further demonstrate GELN aly-miR159a-3p enhances anti-PD-L1 therapy melanoma inhibiting expression recipient bacterial phospholipase C (PLC) increases accumulation docosahexaenoic acid (DHA). An increased level circulating DHA inhibits PD-L1 tumor cells binding promoter subsequently prevents c-myc-initiated transcription PD-L1. Colonization germ-free male mice bacteria from non-responding patients supplemented efficacy compared controls. Our findings reveal previously unknown mechanistic PNP human modulating metabolic pathways.

Language: Английский

Citations

4
Impacts of tissue context on extracellular vesicles‐mediated cancer–host cell communications DOI Creative Commons
Nao Nishida‐Aoki, Takahiro Ochiya

Cancer Science, Journal Year: 2024, Volume and Issue: 115(6), P. 1726 - 1737

Published: March 26, 2024

Abstract Tumor tissue is densely packed with cancer cells, non‐cancerous and ECM, forming functional structures. Cancer cells transfer extracellular vesicles (EVs) to modify surrounding normal into cancer‐promoting establishing a tumor‐favorable environment together other signaling molecules structural components. Such environments largely affect cell properties, so as EV‐mediated cellular communications within tumor tissue. However, current research on EVs focuses analysis of isolated from the liquid phase, including culture supernatants blood draws, 2D‐cultured assays, or systemic analyses animal models for biodistribution. Therefore, we have limited understanding local EV tissues. In this review, discuss need study in physiological context by summarizing findings impacts properties techniques required analysis. likely alter pose physical barriers, interactions, interstitial flows dynamics, introduce varieties types taken up. Utilizing experimental settings spatial analyses, tackle remaining questions cancer–host interactions. Understanding tissues will lead developing interaction‐targeting therapies provide insight interspecies

Language: Английский

Citations

6
Live imaging of paracrine signaling: Advances in visualization and tracking techniques DOI Creative Commons

Eriko Deguchi,

Michiyuki Matsuda, Kenta Terai

et al.

Cell Structure and Function, Journal Year: 2025, Volume and Issue: 50(1), P. 1 - 14

Published: Jan. 1, 2025

Live imaging techniques have revolutionized our understanding of paracrine signaling, a crucial form cell-to-cell communication in biological processes. This review examines recent advances visualizing and tracking factors through four key stages: secretion from producing cells, diffusion extracellular space, binding to target activation intracellular signaling within cells. Paracrine factor can be directly visualized by fluorescent protein tagging ligand, or indirectly the cleavage transmembrane pro-ligands plasma membrane fusion endosomes comprising factors. Diffusion has been studied using such as fluorescence correlation spectroscopy (FCS), recovery after photobleaching (FRAP), decay photoactivation (FDAP), single-molecule tracking. Binding cells various biosensors, including GPCR-activation-based (GRAB) sensors Förster resonance energy transfer (FRET) probes for receptor tyrosine kinases. Finally, is monitored biosensors second messengers, transcription factors, so on. In addition tools, also highlights emerging optogenetic chemogenetic tools triggering release which essential associating outcomes during bioimaging signaling.Key words: live imaging, optogenetics, chemogenetics.

Language: Английский

Citations

0
Small extracellular vesicles: the origins, current status, future prospects, and applications DOI Creative Commons
Xinyi Zhou, Jin Huang,

Dianqi Zhang

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 17, 2025

Small extracellular vesicles (sEVs) are membrane-bound with a size of less than 200 nm, released by cells. Due to their relatively small molecular weight and ability participate in intercellular communication, sEVs can serve not only as carriers biomarkers for disease diagnosis but also effective drug delivery agents. Furthermore, these involved regulating the onset progression various diseases, reflecting physiological functional states This paper introduces classification vesicles, focus on extraction identification significant role repair, diagnosis, communication. Additionally, addresses engineering modification provide reference enhanced understanding application.

Language: Английский

Citations

0
Liposome‐based in situ antigen‐modification strategy for “universal” T‐cell‐receptor engineered T cell in cancer immunotherapy DOI Creative Commons
Qin Wang, Rui Peng,

Haoyue Qi

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(7)

Published: July 1, 2024

Abstract T‐cell receptor (TCR) engineered therapy, unlike chimeric antigen relies on the inherent ability of TCRs to detect a wider variety antigenic epitopes, such as protein fragments found internally or externally cells. Hence, TCR‐T‐cell therapy offers broader possibilities for treating solid tumors. However, because complicated process identifying specific peptides, their clinical application still encounters significant challenges. Thus, we aimed establish novel “universal” TCR‐T “artificial expression” technique that involves delivery tumor cells using DSPE‐PEG‐NY‐ESO‐1 157‐165 liposomes (NY‐ESO‐1 Lips) express TCR‐T‐cell‐specific recognition targets. In vitro well in vivo studies revealed they could accumulate efficiently area and deliver target antigens activate tumor‐specific cytotoxic immune response. NY‐ESO‐1 when used combination, dramatically curbed progression extended longevity mice. Additionally, PD‐1 blockage enhanced therapeutic effect aforementioned therapy. conclusion, Lips “cursed” by enabling expression surface. This innovative presents groundbreaking approach widespread utilization treatment.

Language: Английский

Citations

3
Mechanobiology of 3D cell confinement and extracellular crowding DOI Creative Commons

Gabriela Da Silva André,

Céline Labouesse

Biophysical Reviews, Journal Year: 2024, Volume and Issue: 16(6), P. 833 - 849

Published: Oct. 23, 2024

Cells and tissues are often under some level of confinement, imposed by the microenvironment neighboring cells, meaning that there limitations to cell size, volume changes, fluid exchanges. 3D culture, increasingly used for both single cells organoids, inherently impose levels confinement absent in 2D systems. It is thus key understand how different influences survival, function, fate. well known mechanical properties microenvironment, such as stiffness stress relaxation, important activating mechanosensitive pathways, these responsive conditions. In this review, we look at low, intermediate, high modulate activation mechanobiology tumor spheroids, with a specific focus on microwells, elastic, or viscoelastic scaffolds. addition, confining can drastically limit cellular communication healthy diseased tissues, due extracellular crowding. We discuss potential implications crowding molecular transport, matrix deposition, transport. Understanding sense respond various should inform design engineered matrices recapitulate physical tissues.

Language: Английский

Citations

3
Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics DOI Creative Commons
Stephanie R. Jackson, Joseph P. Flemming,

Kübra Karagoz

et al.

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(11)

Published: Oct. 30, 2024

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue achieve or seek approval, setbacks are often attributed a lack efficacy, failure clinical endpoints, dose-limiting toxicities. Successful efforts have characterized by the development therapeutics designed specifically deliver optimal dosing tumour cells while minimizing off-target toxicity. Much effort devoted rational design application synthetic nanoparticles serve as targeted therapeutic delivery vehicles. Several challenges successful this modality vehicles include induction protracted immune response that results in their rapid systemic clearance, manufacturing cost, stability, biocompatibility. Extracellular vesicles (EVs) heterogeneous class endogenous biologically produced lipid bilayer mediate intercellular communication carrying bioactive macromolecules capable modifying cellular phenotypes local distant cells. By genetic, chemical, metabolic methods, extracellular can be engineered display targeting moieties on surface transporting specific cargo modulate pathological processes following uptake target cell populations. This review will survey types EVs, composition cargoes, strategies employed increase targeting, uptake, release, potential

Language: Английский

Citations

2