Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy.
10.1016/j.apsb.2025.04.013
- Author:
Jian ZHAO
1
;
Xinyan LV
2
;
Qi LU
1
;
Kaiyuan WANG
1
;
Lili DU
1
;
Xiaoyuan FAN
1
;
Fei SUN
1
;
Fengxiang LIU
1
;
Zhonggui HE
1
;
Hao YE
3
;
Jin SUN
1
Author Information
1. Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
3. Multi-Scale Robotics Lab (MSRL), Institute of Robotics & Intelligent Systems (IRIS), ETH Zurich, Zurich 8092, Switzerland.
- Publication Type:Journal Article
- Keywords:
Biological carrier systems;
CD47;
Deep penetration;
Enhance adhesion;
Exosome spheres;
P-selectin;
Phosphatidylserine;
Prolong blood circulation time
- From:
Acta Pharmaceutica Sinica B
2025;15(7):3756-3766
- CountryChina
- Language:English
-
Abstract:
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.
