Nanoparticles Targeting the Tumor Microenvironment for the Treatment of Osteosarcoma: Recent Progress and Perspectives

Guohui Liang,1 Wei Wang,1 Chao Li,2 Binlong Zhong,1 Lei Zhao,1 Zhicai Zhang,1 Jianxiang Liu1 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Zigong Fourth People’s Hospital, Zigong, 643000, People’s Republic of ChinaCorrespondence: Jianxiang Liu, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Email [email protected]: Osteosarcoma (OS) is the most common primary malignant bone tumor, with two incidence peaks: one in adolescence and the other in older individuals. Despite significant research, patient prognosis has not substantially improved in recent decades because of a limited understanding of its pathogenesis and a lack of innovation in treatment approaches. The tumor microenvironment (TME) is a rapidly evolving area of cancer therapy, offering critical insights into the dynamics of osteosarcoma development at the cellular and molecular levels. This study also provides valuable guidance for the development of novel therapeutic strategies. To date, a broad array of nanomedicines have been engineered to target specific ligands within the OS TME. Compared with conventional chemotherapeutic agents, these nanomedicines can substantially enhance drug delivery efficiency while minimizing off-target side effects. In this review, we focus on nanomedicines that target the TME of osteosarcoma. We first explore the core components of the OS TME, which include osteoblasts, mesenchymal stem cells, the vascular microenvironment, and immune cells. Subsequently, we delve into the latest advances and biomedical applications of nanodrug delivery systems engineered specifically for targeting the TME of osteosarcoma. The findings of this review aim to contribute to improved treatment options and outcomes for osteosarcoma patients.Keywords: osteosarcoma, tumor microenvironment, targeting, nanomedicine, nanoparticles