Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells
Mutant p53 proteins result from missense mutations in the TP53 gene, the most mutated in human cancer, and have been described to contribute to cancer initiation and progression. Therapeutic strategies for targeting mutant p53 proteins in cancer cells are limited and have proved unsuitable for clini...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2067 |
| _version_ | 1797501533885038592 |
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| author | Eduardo García-Garrido Marco Cordani Álvaro Somoza |
| author_facet | Eduardo García-Garrido Marco Cordani Álvaro Somoza |
| author_sort | Eduardo García-Garrido |
| collection | DOAJ |
| description | Mutant p53 proteins result from missense mutations in the TP53 gene, the most mutated in human cancer, and have been described to contribute to cancer initiation and progression. Therapeutic strategies for targeting mutant p53 proteins in cancer cells are limited and have proved unsuitable for clinical application due to problems related to drug delivery and toxicity to healthy tissues. Therefore, the discovery of efficient and safe therapeutic strategies that specifically target mutant p53 remains challenging. In this study, we generated gold nanoparticles (AuNPs) chemically modified with low molecular branched polyethylenimine (bPEI) for the efficient delivery of gapmers targeting p53 mutant protein. The AuNPs formulation consists of a combination of polymeric mixed layer of polyethylene glycol (PEG) and PEI, and layer-by-layer assembly of bPEI through a sensitive linker. These nanoparticles can bind oligonucleotides through electrostatic interactions and release them in the presence of a reducing agent as glutathione. The nanostructures generated here provide a non-toxic and powerful system for the delivery of gapmers in cancer cells, which significantly downregulated mutant p53 proteins and altered molecular markers related to cell growth and apoptosis, thus overcoming chemoresistance to gemcitabine. |
| first_indexed | 2024-03-10T03:19:48Z |
| format | Article |
| id | doaj.art-cb47a68874044483b7e73a8ddf4e131e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:48Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-cb47a68874044483b7e73a8ddf4e131e2023-11-23T10:05:27ZengMDPI AGPharmaceutics1999-49232021-12-011312206710.3390/pharmaceutics13122067Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer CellsEduardo García-Garrido0Marco Cordani1Álvaro Somoza2Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Faraday 9, 28049 Madrid, SpainInstituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Faraday 9, 28049 Madrid, SpainInstituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Faraday 9, 28049 Madrid, SpainMutant p53 proteins result from missense mutations in the TP53 gene, the most mutated in human cancer, and have been described to contribute to cancer initiation and progression. Therapeutic strategies for targeting mutant p53 proteins in cancer cells are limited and have proved unsuitable for clinical application due to problems related to drug delivery and toxicity to healthy tissues. Therefore, the discovery of efficient and safe therapeutic strategies that specifically target mutant p53 remains challenging. In this study, we generated gold nanoparticles (AuNPs) chemically modified with low molecular branched polyethylenimine (bPEI) for the efficient delivery of gapmers targeting p53 mutant protein. The AuNPs formulation consists of a combination of polymeric mixed layer of polyethylene glycol (PEG) and PEI, and layer-by-layer assembly of bPEI through a sensitive linker. These nanoparticles can bind oligonucleotides through electrostatic interactions and release them in the presence of a reducing agent as glutathione. The nanostructures generated here provide a non-toxic and powerful system for the delivery of gapmers in cancer cells, which significantly downregulated mutant p53 proteins and altered molecular markers related to cell growth and apoptosis, thus overcoming chemoresistance to gemcitabine.https://www.mdpi.com/1999-4923/13/12/2067mutant p53nanomedicinedrug deliverycancer therapygold nanoparticlesnucleic acids |
| spellingShingle | Eduardo García-Garrido Marco Cordani Álvaro Somoza Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells Pharmaceutics mutant p53 nanomedicine drug delivery cancer therapy gold nanoparticles nucleic acids |
| title | Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells |
| title_full | Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells |
| title_fullStr | Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells |
| title_full_unstemmed | Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells |
| title_short | Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells |
| title_sort | modified gold nanoparticles to overcome the chemoresistance to gemcitabine in mutant p53 cancer cells |
| topic | mutant p53 nanomedicine drug delivery cancer therapy gold nanoparticles nucleic acids |
| url | https://www.mdpi.com/1999-4923/13/12/2067 |
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