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Published on: July 12, 2024
A protein nanocontainer targeting epithelial cancers: rational engineering, biochemical characterization, drug
Caroline Ladurantie1, Mathilde Coustets, Georges Czaplicki
1Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 205 Route de Narbonne, BP64182, 31077 Toulouse, France. Laurent.Paquereau@ipbs.fr.
Abstract:
The development of drug delivery and imaging tools is a major challenge in human health, in particular in cancer pathologies. This work describes the optimization of a protein nanocontainer, belonging to the lectin protein family, for its use in epithelial cancer diagnosis and treatment. Indeed, it specifically targets a glycosidic marker, the T antigen, which is known to be characteristic of epithelial cancers. Its quaternary structure reveals a large hydrated inner cavity able to transport small therapeutic molecules. Optimization of the nanocontainer by site directed mutagenesis allowed controlling loading and release of confined drugs. Doxorubicin confinement was followed, both theoretically and experimentally, and provided a proof of concept for the use of this nanocontainer as a vectorization system. In OVCAR-3 cells, a human ovarian adenocarcinoma cell line that expresses the T antigen, the drug was observed to be delivered inside late endosomes/lysosomes. These results show that this new type of vectorization and imaging device opens new exciting perspectives in nano-theranostic approaches.
Insights
Researchers optimized a protein nanocontainer for targeted epithelial cancer diagnosis and treatment. This lectin-based system effectively delivers drugs like doxorubicin to cancer cells, showing promise for nanotheranostics.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Developing effective drug delivery and imaging tools for cancer is crucial.
- Protein nanocontainers offer potential for targeted cancer therapy and diagnosis.
- Specific targeting of cancer markers enhances therapeutic efficacy and reduces side effects.
Purpose of the Study:
- To optimize a lectin protein nanocontainer for epithelial cancer diagnosis and treatment.
- To evaluate its specific targeting of the T antigen, a marker for epithelial cancers.
- To demonstrate its capability for controlled drug loading and release.
Main Methods:
- Site-directed mutagenesis was employed to optimize the protein nanocontainer.
- Doxorubicin confinement and release were studied both theoretically and experimentally.
- The nanocontainer's efficacy was tested in OVCAR-3 cells (human ovarian adenocarcinoma).
Main Results:
- The optimized nanocontainer specifically targets the T antigen found on epithelial cancers.
- Controlled loading and release of doxorubicin were achieved.
- Drug delivery into late endosomes/lysosomes of OVCAR-3 cells was confirmed.
Conclusions:
- The optimized protein nanocontainer serves as a viable drug vectorization system for T antigen-expressing cancers.
- This technology opens new avenues for nano-theranostic applications in cancer care.
- Further development could lead to advanced imaging and therapeutic strategies.
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