Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects

Diringer, Marie‐Charlotte; Coliat, Pierre; Mathieu, Clélia; Laurent, Nina; Mura, Carole; Banerjee, Mainak; Zhu, Chen; Grabowska, Anna; Ritchie, Alison; Clarke, Philip; Bernard, Alexandre; Vit, Claire; Burckel, Hélène; Noel, Georges; Harvey, Peter; Pivot, Xavier; Detappe, Alexandre

Abstract

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre‐clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple‐negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non‐toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono‐fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first‐in‐class therapeutic construct capable of tumor‐specific reoxygenation without associated toxicities.

Citation

Diringer, M., Coliat, P., Mathieu, C., Laurent, N., Mura, C., Banerjee, M., Zhu, C., Grabowska, A., Ritchie, A., Clarke, P., Bernard, A., Vit, C., Burckel, H., Noel, G., Harvey, P., Pivot, X., & Detappe, A. (2023). Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects. Small, 19(12), Article 2205961. https://doi.org/10.1002/smll.202205961

• Journal Article Type: Article
• Acceptance Date: Jan 1, 2023
• Online Publication Date: Jan 1, 2023
• Publication Date: Mar 22, 2023
• Deposit Date: Apr 17, 2023
• Publicly Available Date: Apr 18, 2023
• Journal: Small
• Print ISSN: 1613-6810
• Electronic ISSN: 1613-6829
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 12
• Article Number: 2205961
• DOI: https://doi.org/10.1002/smll.202205961
• Keywords: Drug delivery, liposome, oxygenation, trans sodium crocetinate
• Public URL: https://nottingham-repository.worktribe.com/output/15923861
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/smll.202205961
• Additional Information: Received: 2022-09-28; Published: 2023-01-01