Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy
Abstract Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug‐loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin‐based nanocomposite hydrogel is con...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202305217 |
| _version_ | 1797351411876364288 |
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| author | Rong Liu Qian Liang Jia‐Qi Luo Yu‐Xuan Li Xin Zhang Kelong Fan Jin‐Zhi Du |
| author_facet | Rong Liu Qian Liang Jia‐Qi Luo Yu‐Xuan Li Xin Zhang Kelong Fan Jin‐Zhi Du |
| author_sort | Rong Liu |
| collection | DOAJ |
| description | Abstract Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug‐loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin‐based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin‐loaded human ferritin (Dox@HFn) and oxidized dextran (Dex‐CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH‐sensitive Schiff‐base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti‐programmed death‐1 antibody (αPD‐1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti‐tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti‐CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy. |
| first_indexed | 2024-03-08T13:00:04Z |
| format | Article |
| id | doaj.art-2935d7ae3b3f4a0cb7821a635f043d67 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T13:00:04Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-2935d7ae3b3f4a0cb7821a635f043d672024-01-19T09:27:54ZengWileyAdvanced Science2198-38442024-01-01113n/an/a10.1002/advs.202305217Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer ChemoimmunotherapyRong Liu0Qian Liang1Jia‐Qi Luo2Yu‐Xuan Li3Xin Zhang4Kelong Fan5Jin‐Zhi Du6School of Medicine South China University of Technology Guangzhou 510006 ChinaCAS Engineering Laboratory for Nanozyme National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 ChinaSchool of Medicine South China University of Technology Guangzhou 510006 ChinaSchool of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology Guangzhou 511442 ChinaSchool of Medicine South China University of Technology Guangzhou 510006 ChinaCAS Engineering Laboratory for Nanozyme National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 ChinaSchool of Medicine South China University of Technology Guangzhou 510006 ChinaAbstract Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug‐loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin‐based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin‐loaded human ferritin (Dox@HFn) and oxidized dextran (Dex‐CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH‐sensitive Schiff‐base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti‐programmed death‐1 antibody (αPD‐1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti‐tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti‐CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy.https://doi.org/10.1002/advs.202305217cancer chemoimmunotherapyferritinhydrogeltranscytosistumor penetration |
| spellingShingle | Rong Liu Qian Liang Jia‐Qi Luo Yu‐Xuan Li Xin Zhang Kelong Fan Jin‐Zhi Du Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy Advanced Science cancer chemoimmunotherapy ferritin hydrogel transcytosis tumor penetration |
| title | Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy |
| title_full | Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy |
| title_fullStr | Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy |
| title_full_unstemmed | Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy |
| title_short | Ferritin‐Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy |
| title_sort | ferritin based nanocomposite hydrogel promotes tumor penetration and enhances cancer chemoimmunotherapy |
| topic | cancer chemoimmunotherapy ferritin hydrogel transcytosis tumor penetration |
| url | https://doi.org/10.1002/advs.202305217 |
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