https://doi.org/10.1016/j.apsb.2025.04.013
This new article publication from
Acta Pharmaceutica Sinica B, discusses the use of 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 efficiently. However, challenges remain, cells’ large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, the authors of this article 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 demonstrates 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.
Keywords: Biological carrier systems, Exosome spheres, Phosphatidylserine, CD47, Prolong blood circulation time, P-selectin, Enhance adhesion, Deep penetration
Graphical Abstract: available at
https://ars.els-cdn.com/content/image/1-s2.0-S2211383525002667-ga1_lrg.jpg
SPPexD combined with PD-L1 monoclonal antibody regulated the tumor immune microenvironment. SPPexD significantly increased the blood circulation time and adhesion ability of exosomes to tumor cells. Combined with PD-L1 monoclonal antibody could significantly inhibit tumor growth.
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The Journal of the
Institute of Materia Medica, the Chinese Academy of Medical Sciences and the
Chinese Pharmaceutical Association.
For more information please visit
https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/
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CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
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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, Volume 15, Issue 7, 2025, Pages 3756-3766, ISSN 2211-3835,
https://doi.org/10.1016/j.apsb.2025.04.013