Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma

Abstract

Jia-Xin Cai,1– 3,* Ji-Hua Liu,1– 3,* Jun-Yong Wu,1– 3 Yong-Jiang Li,1– 3 Xiao-Han Qiu,1– 3 Wen-Jie Xu,1– 3 Ping Xu,1,2 Da-Xiong Xiang1– 3 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Xu; Da-Xiong Xiang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email [email protected]; [email protected]: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.Methods: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice.Results: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues.Conclusion: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.Keywords: biomimetic nano-drug delivery system, osteosarcoma, paclitaxel, targeted therapy

Keywords

• biomimetic nano-drug delivery system
• osteosarcoma
• paclitaxel
• targeted therapy