ArticleProceedings of the National Academy of Sciences of the United States of America2020
Oxaliplatin Pt(IV) prodrugs conjugated to gadolinium-texaphyrin as potential antitumor agents.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Profiling the Preclinical Pharmacokinetics and Biodistribution of a Platinum(IV)-Based Oxaliplatin Prodrug OxaliTEX and Their Significance to Antitumor Response.Molecular pharmaceutics · 2025Article
- Advances in applied supramolecular technologies 2021-2025.Chemical Society reviews · 2025Review
- Synthesis and Characterization of Thallium-Texaphyrin Nanoparticles and Their Assessment as Potential Delivery Systems for Auger Electron-EmittingMolecular pharmaceutics · 2025Article
- Recent Advances on Pt-Based Compounds for Theranostic Applications.Molecules (Basel, Switzerland) · 2024Review
- Sequential dual-locking strategy using photoactivated Pt(IV)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization.Acta pharmaceutica Sinica. B · 2024Article
- A colorimetric approach for monitoring the reduction of platinum(iv) complexes in aqueous solution.New journal of chemistry = Nouveau journal de chimie · 2024Article
- Investigation of Siderophore-Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo.ACS infectious diseases · 2024Article
- Strategies for the development of stimuli-responsive small molecule prodrugs for cancer treatment.Frontiers in pharmacology · 2024Review
- Texaphyrin-Based Calcium Sensor for Multimodal Imaging.ACS sensors · 2023Article
- Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures.Nanoscale · 2023Article
- An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy.Science advances · 2023Article
- Oxali(IV)Fluors: Fluorescence Responsive Oxaliplatin(IV) Complexes Identify a Hypoxia-Dependent Reduction in Cancer Cells.Journal of the American Chemical Society · 2023Article
- Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy.Nature communications · 2023Article
- Promising heterometallic compounds as anticancer agents: Recent studies in vivo.Current opinion in chemical biology · 2023Review
- A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Lanthanide porphyrinoids as molecular theranostics.Chemical Society reviews · 2022Review
- Controlled assembly of a bicyclic porphyrinoid and its 3-dimensional boron difluoride arrays.Chemical science · 2022Article
- Challenges and opportunities in the development of metal-based anticancer theranostic agents.Bioscience reports · 2022Review
- Profile of Jonathan L. Sessler.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
18 authors.
Funding
Abstract
Described here is the development of gadolinium(III) texaphyrin-platinum(IV) conjugates capable of overcoming platinum resistance by 1) localizing to solid tumors, 2) promoting enhanced cancer cell uptake, and 3) reactivating p53 in platinum-resistant models. Side by side comparative studies of these Pt(IV) conjugates to clinically approved platinum(II) agents and previously reported platinum(II)-texaphyrin conjugates demonstrate that the present Pt(IV) conjugates are more stable against hydrolysis and nucleophilic attack. Moreover, they display high potent antiproliferative activity in vitro against human and mouse cell cancer lines. Relative to the current platinum clinical standard of care (SOC), a lead Gd(III) texaphyrin-Pt(IV) prodrug conjugate emerging from this development effort was found to be more efficacious in subcutaneous (s.c.) mouse models involving both cell-derived xenografts and platinum-resistant patient-derived xenografts. Comparative pathology studies in mice treated with equimolar doses of the lead Gd texaphyrin-Pt(IV) conjugate or the US Food and Drug Administration (FDA)-approved agent oxaliplatin revealed that the conjugate was better tolerated. Specifically, the lead could be dosed at more than three times (i.e., 70 mg/kg per dose) the tolerable dose of oxaliplatin (i.e., 4 to 6 mg/kg per dose depending on the animal model) with little to no observable adverse effects. A combination of tumor localization, redox cycling, and reversible protein binding is invoked to explain the relatively increased tolerability and enhanced anticancer activity seen in vivo. On the basis of the present studies, we conclude that metallotexaphyrin-Pt conjugates may have substantial clinical potential as antitumor agents.
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