Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer
Celastrol (Cel) is a potential anticancer therapeutic candidate, but its limited practical applicability is due to its low solubility, poor tumor selectivity, and cytotoxicity. Clinically, ginsenoside Rg3 (RG3) is typically combined with chemotherapy to enhance antitumor effects and reduce side effe...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2025.2464189 |
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| author | Zheng Zhang Jiaxing Wang Xiaofang Li Lingzhou Zhao Junwei Zhao Mengjiao Su Xiangxiang Wu Huahui Zeng |
| author_facet | Zheng Zhang Jiaxing Wang Xiaofang Li Lingzhou Zhao Junwei Zhao Mengjiao Su Xiangxiang Wu Huahui Zeng |
| author_sort | Zheng Zhang |
| collection | DOAJ |
| description | Celastrol (Cel) is a potential anticancer therapeutic candidate, but its limited practical applicability is due to its low solubility, poor tumor selectivity, and cytotoxicity. Clinically, ginsenoside Rg3 (RG3) is typically combined with chemotherapy to enhance antitumor effects and reduce side effects. Herein, we developed novel pH-sensitive prodrug nanoparticles (NPs) containing RG3 and Cel for the synergistic treatment of pancreatic cancer (PC). Amphiphilic prodrug, a PEGylated chitosan oligosaccharide coupled with RG3 via Schiff base bond, was self-assembled with hydrophobic Cel into NPs with drug loadings of 2.12% (Cel) and 1.63% (RG3). NPs exhibited a suitable particle size of 124.01 nm, zeta potential of −39.89 mV and good physical stability. In addition, NPs also showed a controlled drug release when the Schiff base bonds were hydrolyzed in the acidic environment. In Pan02 tumor-bearing mice, NPs exhibited a high accumulation in tumor tissues and prolonged blood circulation time. Furthermore, NPs could more effectively inhibit tumor growth and reduce systemic toxicity, compared with the free Cel, RG3, prodrug, and Cel + RG3. The results indicated that the NPs could provide a safe and promising nanoplatform for PC therapy. |
| format | Article |
| id | doaj-art-75196ffc77a844ceb2dda637875b7b3a |
| institution | DOAJ |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-75196ffc77a844ceb2dda637875b7b3a2025-08-20T03:21:31ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642025-12-0132110.1080/10717544.2025.2464189Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancerZheng Zhang0Jiaxing Wang1Xiaofang Li2Lingzhou Zhao3Junwei Zhao4Mengjiao Su5Xiangxiang Wu6Huahui Zeng7Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Core Unit of National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, ChinaCelastrol (Cel) is a potential anticancer therapeutic candidate, but its limited practical applicability is due to its low solubility, poor tumor selectivity, and cytotoxicity. Clinically, ginsenoside Rg3 (RG3) is typically combined with chemotherapy to enhance antitumor effects and reduce side effects. Herein, we developed novel pH-sensitive prodrug nanoparticles (NPs) containing RG3 and Cel for the synergistic treatment of pancreatic cancer (PC). Amphiphilic prodrug, a PEGylated chitosan oligosaccharide coupled with RG3 via Schiff base bond, was self-assembled with hydrophobic Cel into NPs with drug loadings of 2.12% (Cel) and 1.63% (RG3). NPs exhibited a suitable particle size of 124.01 nm, zeta potential of −39.89 mV and good physical stability. In addition, NPs also showed a controlled drug release when the Schiff base bonds were hydrolyzed in the acidic environment. In Pan02 tumor-bearing mice, NPs exhibited a high accumulation in tumor tissues and prolonged blood circulation time. Furthermore, NPs could more effectively inhibit tumor growth and reduce systemic toxicity, compared with the free Cel, RG3, prodrug, and Cel + RG3. The results indicated that the NPs could provide a safe and promising nanoplatform for PC therapy.https://www.tandfonline.com/doi/10.1080/10717544.2025.2464189Ginsenoside Rg3celastrolprodrugnanoparticlespancreatic cancer |
| spellingShingle | Zheng Zhang Jiaxing Wang Xiaofang Li Lingzhou Zhao Junwei Zhao Mengjiao Su Xiangxiang Wu Huahui Zeng Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer Drug Delivery Ginsenoside Rg3 celastrol prodrug nanoparticles pancreatic cancer |
| title | Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| title_full | Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| title_fullStr | Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| title_full_unstemmed | Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| title_short | Synergistic effect of pH-sensitive PEGylated RG3-chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| title_sort | synergistic effect of ph sensitive pegylated rg3 chitosan prodrug nanoparticles encapsulated celastrol on pancreatic cancer |
| topic | Ginsenoside Rg3 celastrol prodrug nanoparticles pancreatic cancer |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2025.2464189 |
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