Natural, Engineered, and Hybrid Platelet Membrane–Based Nanotherapeutics for Inflammatory Diseases

Boyuan Liu,1,* Yongjie Wang,1– 3,* Weiquan Gong,1 Song Han,1 Zhenshan Lv,1 Zilin Zhang,1 Jinwei Qi,1 Aijun Song,1 Zongyuan Yang,1 Longfei Duan,1 Tianhui Zhang,1 Zhenyu Wang1 1Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Orthopedics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China; 3Department of Orthopaedics, Wenzhou Medical University Affiliated Taizhou Central Hospital, Taizhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenyu Wang, Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Email [email protected]: Nanotherapeutics based on platelet membranes represent a new and advanced biomimetic approach in nanomedicine. By covering synthetic nanoparticle cores with natural platelet membranes, these platforms ingeniously combine the multifaceted biointerfacing abilities of platelets, such as long circulation, immune evasion, and targeting of inflamed tissues, with the many functions of engineered cores. This review systematically summarizes recent advances in the design and application of nanotherapeutics, categorizing them into three platforms: those derived from natural platelet membranes, those utilizing engineered platelet membranes for enhanced targeting or drug loading, and those employing hybrid membranes fused with other cell types to combine complementary functionalities. We emphasize their therapeutic efficacy in various inflammatory diseases such as atherosclerosis, ischemic injury (stroke and myocardial infarction), rheumatoid arthritis, microbial infections, and the tumor inflammatory microenvironment. Finally, we discuss the translational potential and current challenges of this technology and provide a critical perspective on its future development in precision medicine. Keywords: platelet membrane, engineered platelet, hybrid membrane, inflammation, nanotherapy