ArticleAdvanced pharmaceutical bulletin2025
MUC1-Driven Guanylin Gene Delivery via Succinylated PEI-9 Nanocarrier for Colorectal Cancer Treatment: An in Silico and In vitro Study.
Article in Advanced pharmaceutical bulletin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Addressing colorectal cancer (CRC) poses a significant challenge, demanding the precise delivery of therapeutic agents to eliminate cancer cells while minimizing the impact on healthy cells. The strategic selection of therapeutic targets, the utilization of nanocarriers with optimal efficacy and low toxicity, and the development of gene constructs with targeted expression in cancer cells are crucial aspects of this pursuit. Methods: This study employed a systems biology approach to comprehensively investigate the guanylin hormone-encoding gene (GUCA2A). Exploration encompassed expression patterns across tissues and single cells, clinical endpoints, methylation profiles, mutations, and immune and functional analyses. Subsequently, GUCA2A was identified as a potential target for gain of function studies, leading to its amplification and cloning into gene constructs featuring both a robust CMV promoter and a cancer-specific MUC1 promoter. The succinylated PEI-9, characterized by low toxicity and high gene transfer efficiency, was then fabricated and characterized on HCT-116 cancer cells and normal Vero cell lines. Results: systems biology studies revealed guanylin's aberrant expression patterns, methylation variations, and mutational changes as well as its remarkable association with immune engagement and poor survival outcomes in CRC. Moreover, SPEI-9 was introduced as a highly efficient and safe nanocarrier for gene delivery purposes. Additionally, in vitro studies revealed that both guanylin-expressing gene constructs exhibited the potential to inhibit cell growth and proliferation, inducing apoptosis, suppressing cell migration, and curtailing colony formation. Notably, these effects were more robust but non-specific in cancer cells treated with constructs containing the CMV general promoter, while induction via the MUC1 promoter was more specific. Conclusion: A genetic construct featuring strong universal CMV and specific MUC1 promoter, expressing the guanylin peptide hormone, demonstrated highly effective and specific anticancer effects when transfected with nanocarriers characterized by high efficiency and low cytotoxicity. This nano-system holds promising implications for future targeted CRC therapy clinical trials.
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Registered trials
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