Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy
Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors effici...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525002667 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849467216754376704 |
|---|---|
| author | Jian Zhao Xinyan Lv Qi Lu Kaiyuan Wang Lili Du Xiaoyuan Fan Fei Sun Fengxiang Liu Zhonggui He Hao Ye Jin Sun |
| author_facet | Jian Zhao Xinyan Lv Qi Lu Kaiyuan Wang Lili Du Xiaoyuan Fan Fei Sun Fengxiang Liu Zhonggui He Hao Ye Jin Sun |
| author_sort | Jian Zhao |
| collection | DOAJ |
| description | Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells’ large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery. |
| format | Article |
| id | doaj-art-87d9808f72584130a00818d76f2fe64b |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-87d9808f72584130a00818d76f2fe64b2025-08-20T03:28:25ZengElsevierActa Pharmaceutica Sinica B2211-38352025-07-011573756376610.1016/j.apsb.2025.04.013Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapyJian Zhao0Xinyan Lv1Qi Lu2Kaiyuan Wang3Lili Du4Xiaoyuan Fan5Fei Sun6Fengxiang Liu7Zhonggui He8Hao Ye9Jin Sun10Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, ChinaMulti-Scale Robotics Lab (MSRL), Institute of Robotics & Intelligent Systems (IRIS), ETH Zurich, Zurich 8092, Switzerland; Corresponding authors.Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors.Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells’ large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.http://www.sciencedirect.com/science/article/pii/S2211383525002667Biological carrier systemsExosome spheresPhosphatidylserineCD47Prolong blood circulation timeP-selectin |
| spellingShingle | Jian Zhao Xinyan Lv Qi Lu Kaiyuan Wang Lili Du Xiaoyuan Fan Fei Sun Fengxiang Liu Zhonggui He Hao Ye Jin Sun Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy Acta Pharmaceutica Sinica B Biological carrier systems Exosome spheres Phosphatidylserine CD47 Prolong blood circulation time P-selectin |
| title | Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| title_full | Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| title_fullStr | Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| title_full_unstemmed | Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| title_short | Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| title_sort | engineered platelet derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy |
| topic | Biological carrier systems Exosome spheres Phosphatidylserine CD47 Prolong blood circulation time P-selectin |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525002667 |
| work_keys_str_mv | AT jianzhao engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT xinyanlv engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT qilu engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT kaiyuanwang engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT lilidu engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT xiaoyuanfan engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT feisun engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT fengxiangliu engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT zhongguihe engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT haoye engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy AT jinsun engineeredplateletderivedexosomalspheresforenhancedtumorpenetrationandextendedcirculationinmelanomaimmunotherapy |