A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer
Pancreatic cancers are marked by a highly fibrotic extracellular matrix (ECM) that fosters an immunosuppressive tumor microenvironment (TME), severely limiting the effectiveness of traditional therapies. Emerging evidence suggests that ECM modulation represents a promising strategy to enhance treatm...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007239 |
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| author | Weiting Jiang Wei Deng Qi Chen Huahua Zhang Min Zhu Rongze Wang Yong Wang |
| author_facet | Weiting Jiang Wei Deng Qi Chen Huahua Zhang Min Zhu Rongze Wang Yong Wang |
| author_sort | Weiting Jiang |
| collection | DOAJ |
| description | Pancreatic cancers are marked by a highly fibrotic extracellular matrix (ECM) that fosters an immunosuppressive tumor microenvironment (TME), severely limiting the effectiveness of traditional therapies. Emerging evidence suggests that ECM modulation represents a promising strategy to enhance treatment outcomes in pancreatic cancer. Herein, we developed a polymeric nanovesicle for the co-encapsulation and delivery of gemcitabine and prolyl isomerase Pin1 inhibitor sulfopin (Gem/Sul-NP). The engineered Gem/Sul-NP features a compact size of approximately 50 nm, facilitating improved accumulation and penetration within pancreatic tumor tissues. Additionally, the Gem/Sul-NP demonstrates pH-responsive characteristics, undergoing structural disintegration at the acidic pH of 6.5 to achieve controlled drug release in the TME, thereby facilitating synergistic antitumor effects. Sulfopin functions to inhibit pancreatic stellate cells (PSCs) activation, reducing ECM component secretion and disrupting stromal barriers. Besides, it upregulates the expression of the gemcitabine transporter equilibrative nucleoside transporter 1 (ENT1) on tumor cell membranes, thereby enhancing the cellular uptake of gemcitabine and its chemotherapeutic impact. Our in vivo studies confirmed that Gem/Sul-NP treatment effectively remodeled the immunosuppressive TME. When combined with anti-PD-1 therapy, this approach significantly increased CD8+IFNγ+ T cell infiltration, indicating its potential to create favorable conditions for synergistic chemoimmunotherapy against pancreatic cancers. |
| format | Article |
| id | doaj-art-45f50bc2f9834c9c81dba79aae902e0d |
| institution | Matheson Library |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
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| series | Materials Today Bio |
| spelling | doaj-art-45f50bc2f9834c9c81dba79aae902e0d2025-08-03T04:42:59ZengElsevierMaterials Today Bio2590-00642025-10-0134102153A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancerWeiting Jiang0Wei Deng1Qi Chen2Huahua Zhang3Min Zhu4Rongze Wang5Yong Wang6College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, ChinaCollege of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, ChinaDepartment of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, ChinaCollege of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, ChinaCollege of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, ChinaDepartment of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China; Corresponding author.College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China; Corresponding author.Pancreatic cancers are marked by a highly fibrotic extracellular matrix (ECM) that fosters an immunosuppressive tumor microenvironment (TME), severely limiting the effectiveness of traditional therapies. Emerging evidence suggests that ECM modulation represents a promising strategy to enhance treatment outcomes in pancreatic cancer. Herein, we developed a polymeric nanovesicle for the co-encapsulation and delivery of gemcitabine and prolyl isomerase Pin1 inhibitor sulfopin (Gem/Sul-NP). The engineered Gem/Sul-NP features a compact size of approximately 50 nm, facilitating improved accumulation and penetration within pancreatic tumor tissues. Additionally, the Gem/Sul-NP demonstrates pH-responsive characteristics, undergoing structural disintegration at the acidic pH of 6.5 to achieve controlled drug release in the TME, thereby facilitating synergistic antitumor effects. Sulfopin functions to inhibit pancreatic stellate cells (PSCs) activation, reducing ECM component secretion and disrupting stromal barriers. Besides, it upregulates the expression of the gemcitabine transporter equilibrative nucleoside transporter 1 (ENT1) on tumor cell membranes, thereby enhancing the cellular uptake of gemcitabine and its chemotherapeutic impact. Our in vivo studies confirmed that Gem/Sul-NP treatment effectively remodeled the immunosuppressive TME. When combined with anti-PD-1 therapy, this approach significantly increased CD8+IFNγ+ T cell infiltration, indicating its potential to create favorable conditions for synergistic chemoimmunotherapy against pancreatic cancers.http://www.sciencedirect.com/science/article/pii/S2590006425007239ChemoimmunotherapyOrthotopic pancreatic cancerPancreatic stellate cellsPolymeric nanovesicleTumor microenvironment remodeling |
| spellingShingle | Weiting Jiang Wei Deng Qi Chen Huahua Zhang Min Zhu Rongze Wang Yong Wang A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer Materials Today Bio Chemoimmunotherapy Orthotopic pancreatic cancer Pancreatic stellate cells Polymeric nanovesicle Tumor microenvironment remodeling |
| title | A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| title_full | A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| title_fullStr | A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| title_full_unstemmed | A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| title_short | A polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| title_sort | polymeric nanovesicle delivers sulfopin and gemcitabine to remodel tumor microenvironment for enhanced chemoimmunotherapy against orthotopic pancreatic cancer |
| topic | Chemoimmunotherapy Orthotopic pancreatic cancer Pancreatic stellate cells Polymeric nanovesicle Tumor microenvironment remodeling |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007239 |
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