Huan Bao,1,* Yun Chen,2,* Yonghui Zong,3 Ketao Jin,4 Huanrong Lan5 

1Department of Neurosurgery, Jiashan First People’s Hospital, Jiashan First People’s Hospital Luoxing Branch, Jiashan, Zhejiang, 314100, People’s Republic of China; 2Department of Colorectal Surgery, Xinchang People’s Hospital, Affiliated Xinchang Hospital, Wenzhou Medical University, Xinchang, Zhejiang, 312500, People’s Republic of China; 3Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 4Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of China; 5Department of Surgical Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ketao Jin, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 54, Youdian Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Email jinketao2001@zju.edu.cn Huanrong Lan, Department of Surgical Oncology, Hangzhou Cancer Hospital, No. 34, Yanguan Road, Hangzhou, Zhejiang, 310002, People’s Republic of China, Email lanhr2018@163.com

Abstract: Bone Morphogenetic Proteins might be the most prospective in glioma treatment because of the facts that they can differentiate glioma cells, inhibit tumor growth and manage glioma stem cells. Its clinical application is hindered by several challenges, including limited permeability across the blood–brain barrier, which impedes effective delivery to the central nervous system; high susceptibility to enzymatic degradation, which compromises stability and therapeutic efficacy; and nonselective binding, which reduces specificity and may result in unintended off-target effects. This review systematically covers the advanced BMP delivery systems such as nanoparticles, smart carriers, gene therapy, and exosome-based system. Hydrogels, scaffolds, and microspheres’ local delivery methods are also discussed as prospective options. The in vitro studies reveal that BMPs are effective and using in vivo glioma models there is also evidence of the effectiveness of BMPs. In addition, new clinical trials reveal concern with safety, tolerability, and therapeutic effects of BMPs, especially their combination with chemotherapy and immunotherapy. BMP specificity and therapeutic performance are further optimized by Personalized medicine and CRISPR/Cas engineering. However, regulatory barriers and product commercialization are challenging issues. This review highlights the need for novel approaches and advanced technologies to address the challenges associated with BMP delivery, aiming to establish BMP-based therapies as an effective treatment strategy for glioma.

Keywords: bone morphogenetic proteins, glioma treatment, blood–brain barrier, nanoparticle-based delivery, gene therapy strategies