Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels
Abstract The main obstacles to the clinical application of the CRISPR/Cas9 system are off-target effects and low delivery efficiency. There is an urgent need to develop new delivery strategies and technologies. Three types of in situ injectable hydrogels with different electrical properties were cre...
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BMC
2025-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03523-7 |
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| author | Meng Li Songli Zhou Suqin Zhang Xingyu Xie Junqi Nie Qi Wang Lixin Ma Yibin Cheng Jingwen Luo |
| author_facet | Meng Li Songli Zhou Suqin Zhang Xingyu Xie Junqi Nie Qi Wang Lixin Ma Yibin Cheng Jingwen Luo |
| author_sort | Meng Li |
| collection | DOAJ |
| description | Abstract The main obstacles to the clinical application of the CRISPR/Cas9 system are off-target effects and low delivery efficiency. There is an urgent need to develop new delivery strategies and technologies. Three types of in situ injectable hydrogels with different electrical properties were created to find the most secure and efficient sustained-release drug delivery system. After in vitro and in vivo comparisons, we found that the positively charged hydrogels had higher cellular uptake, stronger gene editing efficiency, greater cytotoxicity, longer tumor accumulation, and better anti-tumor efficacy than negatively charged and neutral hydrogels. We designed single guide RNA targeting the Y-box binding protein 1 (YB-1) gene and then used it to create a ribonucleoprotein complex with Cas9 protein. Doxorubicin was co-encapsulated into this positively charged hydrogel to create a co-delivery system. By knocking down YB-1, the expression of YB-1 was reduced, inhibiting the growth and migration of melanoma cells. The strategy of combining YB-1 gene editing and intratumoral injection enhanced the therapeutic effect of doxorubicin while reducing side effects. |
| format | Article |
| id | doaj-art-82de00689dda49d7a54519ab892d4981 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-82de00689dda49d7a54519ab892d49812025-08-20T02:39:47ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112010.1186/s12951-025-03523-7Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogelsMeng Li0Songli Zhou1Suqin Zhang2Xingyu Xie3Junqi Nie4Qi Wang5Lixin Ma6Yibin Cheng7Jingwen Luo8State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityDepartment of Thoracic Surgery, Tongji Hospital Affiliated to Tongji Medical College of Huazhong, University of Science & TechnologyState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei UniversityAbstract The main obstacles to the clinical application of the CRISPR/Cas9 system are off-target effects and low delivery efficiency. There is an urgent need to develop new delivery strategies and technologies. Three types of in situ injectable hydrogels with different electrical properties were created to find the most secure and efficient sustained-release drug delivery system. After in vitro and in vivo comparisons, we found that the positively charged hydrogels had higher cellular uptake, stronger gene editing efficiency, greater cytotoxicity, longer tumor accumulation, and better anti-tumor efficacy than negatively charged and neutral hydrogels. We designed single guide RNA targeting the Y-box binding protein 1 (YB-1) gene and then used it to create a ribonucleoprotein complex with Cas9 protein. Doxorubicin was co-encapsulated into this positively charged hydrogel to create a co-delivery system. By knocking down YB-1, the expression of YB-1 was reduced, inhibiting the growth and migration of melanoma cells. The strategy of combining YB-1 gene editing and intratumoral injection enhanced the therapeutic effect of doxorubicin while reducing side effects.https://doi.org/10.1186/s12951-025-03523-7CRISPR/Cas9HydrogelPolyaminesIntratumoral injectionYB-1 |
| spellingShingle | Meng Li Songli Zhou Suqin Zhang Xingyu Xie Junqi Nie Qi Wang Lixin Ma Yibin Cheng Jingwen Luo Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels Journal of Nanobiotechnology CRISPR/Cas9 Hydrogel Polyamines Intratumoral injection YB-1 |
| title | Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels |
| title_full | Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels |
| title_fullStr | Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels |
| title_full_unstemmed | Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels |
| title_short | Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels |
| title_sort | transdermal delivery of crispr cas9 mediated melanoma gene therapy via polyamines modified thermosensitive hydrogels |
| topic | CRISPR/Cas9 Hydrogel Polyamines Intratumoral injection YB-1 |
| url | https://doi.org/10.1186/s12951-025-03523-7 |
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