Long-acting bioengineered platelets with internal doxorubicin loaded and external quercetin liposomes anchored for post-surgical tumor therapy

Abstract

Due to its natural tumor targeting ability, platelet-based drug delivery platform shows the great potential for tumor targeted treatment. However, both limited in vitro storage stability and rapid in vivo clearance rate severely restrict its clinical application. Here, utilizing the spatial structure of platelets precisely, chemotherapy drug doxorubicin (Dox) and liposomes-containing quercetin (Que) are loaded inside and anchored outside platelets, respectively, for establishing the engineered platelet platform (PDQLs). Dox plays the important role in inhibiting tumor growth, while Que mainly inhibits platelet apoptosis through activating serine/threonine protein kinase. PDQLs show the strong ability to resist external stimulation and physical damage. After being stored at room temperature for 4 days, more than 70 % of the platelets remain active. Given the natural wound tropism and tumor targeting abilities, the tumor accumulation of PDQLs is 1.02-fold higher than that of the solution. Base on the stealth characteristics of platelets and the continuous action of Que, PDQLs exhibit 10.63-fold increase area under the curve of solution. PDQLs can balance the anti-tumor recurrence and metastasis efficacy after surgery and safety. Our findings open a promising perspective and new sights for the development of bioengineered platelet platform in clinical application.