A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy
Surgery combined with systemic chemotherapy is currently the main modality of cancer treatment. However, the development of cancer multidrug resistance and inevitable surgical residual lesions lead to high rates of cancer recurrence and mortality. Meanwhile, systemic drug toxic side effects and surg...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127523009802 |
| _version_ | 1797347852920291328 |
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| author | Ying Wang Zhuowen Hao Bingshu Li Jianming Tang Zihui Zhang Zhi Wang Lian Yang Jiaxin Peng Jingfeng Li Li Hong |
| author_facet | Ying Wang Zhuowen Hao Bingshu Li Jianming Tang Zihui Zhang Zhi Wang Lian Yang Jiaxin Peng Jingfeng Li Li Hong |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Surgery combined with systemic chemotherapy is currently the main modality of cancer treatment. However, the development of cancer multidrug resistance and inevitable surgical residual lesions lead to high rates of cancer recurrence and mortality. Meanwhile, systemic drug toxic side effects and surgical bleeding complications seriously reduce the quality of life of patients. To avoid cancer multidrug resistance and comprehensively optimize cancer treatment, this work provides a novel injectable cell penetrating peptide octa-arginine (R8)-modified RADA16 (RR) self-assembling peptide nanofiber hydrogel as an anticancer drug carrier for multidrug-resistant cancer therapy. In RR hydrogel, highly compatible RADA16 functions as the β-sheet-based self-assembling backbone which tightly adheres to cancer tissue, prevents postoperative bleeding, and sustainedly releases anticancer drugs for long-term effects. The introduced R8 motifs endow RR hydrogel with the capacity to selectively kill cancer cells and reverse cancer multidrug resistance, which minimally impact normal tissue cells. Specifically, R8 motifs on the hydrogel scaffold selectively interfere with cancer cell membranes, increase drug uptake and penetration into cancer cells and tissues by enhancing multiple internalization pathways, and reduce drug efflux by inhibiting P-gp and BCRP multidrug-resistant transporters. Therefore, this study provides a multifunctional hydrogel material with strong potential for multidrug-resistant cancer clinical translation. |
| first_indexed | 2024-03-08T11:54:55Z |
| format | Article |
| id | doaj.art-eaffb4f65a3f4f38abd2b418ebb5ebbc |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-03-08T11:54:55Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-eaffb4f65a3f4f38abd2b418ebb5ebbc2024-01-24T05:16:25ZengElsevierMaterials & Design0264-12752024-01-01237112564A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapyYing Wang0Zhuowen Hao1Bingshu Li2Jianming Tang3Zihui Zhang4Zhi Wang5Lian Yang6Jiaxin Peng7Jingfeng Li8Li Hong9Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Corresponding authors.Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Corresponding authors.Surgery combined with systemic chemotherapy is currently the main modality of cancer treatment. However, the development of cancer multidrug resistance and inevitable surgical residual lesions lead to high rates of cancer recurrence and mortality. Meanwhile, systemic drug toxic side effects and surgical bleeding complications seriously reduce the quality of life of patients. To avoid cancer multidrug resistance and comprehensively optimize cancer treatment, this work provides a novel injectable cell penetrating peptide octa-arginine (R8)-modified RADA16 (RR) self-assembling peptide nanofiber hydrogel as an anticancer drug carrier for multidrug-resistant cancer therapy. In RR hydrogel, highly compatible RADA16 functions as the β-sheet-based self-assembling backbone which tightly adheres to cancer tissue, prevents postoperative bleeding, and sustainedly releases anticancer drugs for long-term effects. The introduced R8 motifs endow RR hydrogel with the capacity to selectively kill cancer cells and reverse cancer multidrug resistance, which minimally impact normal tissue cells. Specifically, R8 motifs on the hydrogel scaffold selectively interfere with cancer cell membranes, increase drug uptake and penetration into cancer cells and tissues by enhancing multiple internalization pathways, and reduce drug efflux by inhibiting P-gp and BCRP multidrug-resistant transporters. Therefore, this study provides a multifunctional hydrogel material with strong potential for multidrug-resistant cancer clinical translation.http://www.sciencedirect.com/science/article/pii/S0264127523009802Self-assembling peptide hydrogelCell penetrating peptideCancer multidrug resistanceControlled releaseSelective cytotoxicity |
| spellingShingle | Ying Wang Zhuowen Hao Bingshu Li Jianming Tang Zihui Zhang Zhi Wang Lian Yang Jiaxin Peng Jingfeng Li Li Hong A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy Materials & Design Self-assembling peptide hydrogel Cell penetrating peptide Cancer multidrug resistance Controlled release Selective cytotoxicity |
| title | A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy |
| title_full | A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy |
| title_fullStr | A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy |
| title_full_unstemmed | A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy |
| title_short | A novel octa-arginine-modified injectable self-assembling peptide hydrogel for multidrug-resistant cancer therapy |
| title_sort | novel octa arginine modified injectable self assembling peptide hydrogel for multidrug resistant cancer therapy |
| topic | Self-assembling peptide hydrogel Cell penetrating peptide Cancer multidrug resistance Controlled release Selective cytotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0264127523009802 |
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