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Updated: Aug 19, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer
C Pinto-Díez1, R Ferreras-Martín1, R Carrión-Marchante1
1Grupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, Spain.
Abstract:
Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.
Insights
A newly optimized aptamer, apMNKQ2, effectively targets MNK1b in breast cancer cells. This G-quadruplex aptamer reduces tumor growth and metastasis in preclinical models, showing potential as a novel anti-cancer therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Breast cancer is a leading cause of cancer death globally, with Mitogen-activated protein kinase-interacting kinases (MNKs) implicated in oncogenesis.
- The truncated MNK1b isoform exhibits higher constitutive activity and is overexpressed in various cancers.
- Aptamers offer therapeutic advantages, and a specific aptamer, apMNK2F, targeting MNK1b was previously developed.
Purpose of the Study:
- To optimize the apMNK2F aptamer for enhanced stability and reduced size.
- To evaluate the efficacy of the optimized aptamer, apMNKQ2, against breast cancer in vitro and in vivo.
Main Methods:
- Aptamer optimization through sequence modification and stability assessment.
- In vitro assays to assess inhibition of proliferation, colony formation, migration, and invasion in breast cancer cells.
- In vivo studies using murine models to evaluate tumor volume and metastasis reduction.
Main Results:
- The optimized aptamer, apMNKQ2, demonstrated significant inhibition of proliferation, colony formation, migration, and invasion in breast cancer cells.
- In preclinical murine models, apMNKQ2 effectively reduced tumor volume and the number of metastases.
- Sequence analysis of the original aptamer predicted two G-quadruplex structures, which were likely maintained or utilized in the optimized version.
Conclusions:
- The optimized aptamer apMNKQ2 shows potent anti-cancer activity against breast cancer.
- apMNKQ2 exhibits efficacy in reducing tumor growth and metastasis in vivo.
- apMNKQ2 represents a promising candidate for future development as an anti-tumor drug.
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