Issue 7, 2024

Mitochondrial topoisomerase 1 targeted anticancer therapy using irinotecan encapsulated mesoporous MIL-101(Fe) synthesized via a vapour assisted method

Abstract

Mitochondrial topisomerase 1 (Top1mt) is critical for mtDNA replication, transcription, and energy production. Here, we investigate the carrier-mediated targeted delivery of the anticancer drug irinotecan into the mitochondria to selectively trap Top1mt covalent complexes (Top1mtcc) and its role in anticancer therapeutics. We have designed a biocompatible mesoporous metal–organic framework (MOF) material, namely MIL-101(Fe), as the drug delivery carrier that selectively localizes inside mitochondria. In contrast to the traditional way of synthesising MOFs, here we have employed a vapour-assisted solvothermal method for the synthesis of MIL-101(Fe) using terephthalic acid as the organic linker and Fe(III) as the metal source. The advantage of this method is that it recycles the excess solvent (DMF) and reduces the amount of washing solvent. We demonstrate that MIL-101(Fe)-encapsulated irinotecan (MIL-Iri) was selectively targeted towards the mitochondria to poison Top1mtcc in a dose-dependent manner and was achieved at a low nanomolar drug concentration. We provide evidence that Top1mtcc generated by MIL-Iri leads to mtDNA damage in human colon and breast cancer cells and plays a significant role in cellular toxicity. Altogether, this study provides evidence for a new and effective strategy in anticancer chemotherapy.

Graphical abstract: Mitochondrial topoisomerase 1 targeted anticancer therapy using irinotecan encapsulated mesoporous MIL-101(Fe) synthesized via a vapour assisted method

Supplementary files

Article information

Article type
Paper
Submitted
01 Nov 2023
Accepted
09 Jan 2024
First published
11 Jan 2024

Dalton Trans., 2024,53, 3010-3019

Mitochondrial topoisomerase 1 targeted anticancer therapy using irinotecan encapsulated mesoporous MIL-101(Fe) synthesized via a vapour assisted method

A. Ghosh, A. Ghosh, A. Bhattacharyya, R. Mitra, B. B. Das and A. Bhaumik, Dalton Trans., 2024, 53, 3010 DOI: 10.1039/D3DT03654E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements