Mitochondria Localized Anticancer Iridium(III) Prodrugs for Targeted Delivery of Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors and Cytotoxic Iridium(III) Complex DOI
Tejal Dixit,

Monika Negi,

V. Venkatesh

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic oncoprotein overexpressed in several malignancies and acts as one of the promising therapeutic targets for cancer. Even though there are small molecule based Mcl-1 inhibitors reported, delivery inhibitor at target site quite challenging. In this regard, we developed a series mitochondria targeting luminescent cyclometalated iridium(III) prodrugs bearing via ester linkage due to presence protein outer mitochondrial membrane. Among synthesized prodrugs, IrThpy@L2 was found exhibit potent cytotoxicity (IC

Language: Английский

Subcellular visualization: Organelle-specific targeted drug delivery and discovery DOI
Xintian Shao,

Caicai Meng,

Wenjing Song

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114977 - 114977

Published: June 28, 2023

Language: Английский

Citations

38
Transforming Toxicity Assessment through Microphysiology, Bioprinting, and Computational Modeling DOI Open Access

Tamer A. Addissouky

Advances in Clinical Toxicology, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 14

Published: Jan. 1, 2024

Background: Traditional toxicity testing emphasizes animal models with growing concerns regarding predictive capacity, throughput and ethics. Rapid innovation surrounding human cell platforms, bioengineered tissues, omics techniques computational tools offers more modern alternatives aligned expanding knowledge of chemical biological pathways. These disruptive approaches promise immense potential to transform next-generation safety assessment drug development pipelines. Purpose: This review provides clinical researchers an updated, comprehensive perspective across evolving areas focus in new methods analysis latest advances translational context. Main Body: We survey progress two- three-dimensional cultures recapitulating tissue/organ complexity impossible conventional assays. Complementing this, modeling integrates structure-activity relationships, physicochemical properties physiological interactions predict pharmacokinetics silico. Expanding model organisms add further dimensionality demographic relevance. High-throughput imaging technologies unravel mechanisms illuminate biomarkers undetectable by standard measures. Specialized show high addressing toxicodynamic intricacies within disease contexts like diabetes NAFLD. Evaluating traditional medicines phytochemicals likewise represents area growth well-suited for contemporary platforms. Future outlook weighs remarkable advantages reducing demands, enabling precision toxicology links medicine overhauling core risk frameworks. Conclusion: intends catalyze discourse on strategic optimization priorities roadmaps towards fully unlocking the yet still emerging public health these poising transformation sciences centered human-focused models.

Language: Английский

Citations

6
Recapitulating the Drifting and Fusion of Two-Generation Spheroids on Concave Agarose Microwells DOI Open Access

Rong Pan,

Xiaoyan Yang, Ke Ning

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 11967 - 11967

Published: July 26, 2023

Cells with various structures and proteins naturally come together to cooperate in vivo. This study used cell spheroids cultured agarose micro-wells as a 3D model the movement of cells or toward other spheroids. The formation dynamics tumor interactions two batches were studied. results showed that concave bottom micro-well (diameter: 2 mm, depth: mm) prepared from 3% could be interaction cells. initial numbers 5 × 103 cells/well 6 104 all form after 3 days incubation. Adding second batch DU 145 existing spheroid resulted satellite around parental spheroid. Complete fusion generation was observed when formed 1 cells, per well. A higher amount (1 cell/well) led independent 48 h co-culture, suggesting behavior towards depended on factors, such volume number between Human Umbilical Vein Endothelial (HUVECs) modeled micro-wells. HUVECs (3 gather 104, well rather than aggregate their own HUVEC highlights importance analyzing biological properties before designing experimental procedures for sequential further emphasizes significant roles density play determining location

Language: Английский

Citations

11
Doxorubicin-sensitive and -resistant colorectal cancer spheroid models: assessing tumor microenvironment features for therapeutic modulation DOI Creative Commons
Rúben Valente, Sandra Cordeiro, André Luz

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 22, 2023

Introduction: The research on tumor microenvironment (TME) has recently been gaining attention due to its important role in growth, progression, and response therapy. Because of this, the development three-dimensional cancer models that mimic interactions TME structure complexity is great relevance drug development. Methods: This study aimed characterize colorectal spheroids overtime assess how susceptibility or resistance doxorubicin (Dox) inclusion fibroblasts heterotypic influence modulate their secretory activity, namely release extracellular vesicles (EVs), Dox-mediated chemotherapy. Different characteristics were assessed over time, spheroid viability, presence hypoxia, expression hypoxia inflammation-associated genes proteins. Due importance EVs biomarker discovery with impact early diagnostics, prognostics treatment, proteomic profiling released by different 3D was also assessed. Response treatment monitored assessing Dox internalization effects structures cell viability. Results Discussion: results show distinct features are affected both fibroblasts. Fibroblasts can stabilize models, through modulation inflammation levels, as well expressions associated transcripts/proteins, promotes alterations protein profile exhibit EVs. Summarily, increase cell-cell cell-extracellular matrix interactions, making a model understand chemotherapies resistance. induction shown Dox, especially homotypic spheroids, it viability consequently chemoresistance those when exposed Dox. Taken together these highlight finding characterizing resembling more closely vivo tumors modulating

Language: Английский

Citations

11
Method for Culturing and Imaging Homogeneous 3D Cancer Spheroids as a Model for the Uptake of DNA Nanostructures DOI
Emanuela Mensa’, Giampaolo Zuccheri

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 167 - 178

Published: Jan. 1, 2025

Language: Английский

Citations

0
Organoid in Droplet: Production of Uniform Pancreatic Cancer Organoids from Single Cells DOI Creative Commons
Haitao Liu, Tingting Tao, Zhongqiao Gan

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101765 - 101765

Published: April 12, 2025

Language: Английский

Citations

0
Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds DOI Creative Commons

Claire Blanchard,

Alison T. Gomeiz,

Kyle Avery

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 26, 2024

Abstract Background Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult study. Unfortunately, model systems functionally characterize and mechanistically study dynamic responses treatment across coexisting subpopulations cancer cells remain missing need in oncology. Methods Using single cell cloning expansion techniques, we established monoclonal (MCPs) from commercially available epidermal growth factor receptor (EGFR)-mutant non-small lung line. We then used this sensitivity the EGFR inhibitor osimertinib populations within same tumor. Pathway-centered signaling dynamics associated with response morphological characteristics MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated less sensitive pharmacologically inhibited identify target proteins putatively implicated promoting drug resistance. Results demonstrated highly heterogeneous sensitivities osimertinib. Cell viability after increased > 20% compared parental line selected MCPs, whereas decreased by 75% other MCPs. Reduced was detected higher proliferation rates, L858R expression, activation binding partners downstream molecules, expression epithelial-to-mesenchymal transition markers. Levels MCPs’ rates also c-MET IGFR inhibitors. Conclusions represent suitable system biomolecular behaviors preclinical studies test biological mechanisms therapeutics.

Language: Английский

Citations

1
Mitochondria Localized Anticancer Iridium(III) Prodrugs for Targeted Delivery of Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors and Cytotoxic Iridium(III) Complex DOI
Tejal Dixit,

Monika Negi,

V. Venkatesh

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic oncoprotein overexpressed in several malignancies and acts as one of the promising therapeutic targets for cancer. Even though there are small molecule based Mcl-1 inhibitors reported, delivery inhibitor at target site quite challenging. In this regard, we developed a series mitochondria targeting luminescent cyclometalated iridium(III) prodrugs bearing via ester linkage due to presence protein outer mitochondrial membrane. Among synthesized prodrugs, IrThpy@L2 was found exhibit potent cytotoxicity (IC

Language: Английский

Citations

0