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用于靶向胶质瘤的骨形态发生蛋白递送的最新进展:综述更新

Recent Advances in the Delivery of Bone Morphogenetic Proteins for Targeting Glioma: An Updated Review.

作者信息

Bao Huan, Chen Yun, Zong Yonghui, Jin Ketao, Lan Huanrong

机构信息

Department of Neurosurgery, Jiashan First People's Hospital, Jiashan First People's Hospital Luoxing Branch, Jiashan, Zhejiang, 314100, People's Republic of China.

Department of Colorectal Surgery, Xinchang People's Hospital, Affiliated Xinchang Hospital, Wenzhou Medical University, Xinchang, Zhejiang, 312500, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 May 31;20:7093-7112. doi: 10.2147/IJN.S518340. eCollection 2025.

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.

摘要

骨形态发生蛋白可能是治疗神经胶质瘤最具前景的物质,因为它们可以使神经胶质瘤细胞分化、抑制肿瘤生长并调控神经胶质瘤干细胞。其临床应用受到若干挑战的阻碍,包括血脑屏障的通透性有限,这妨碍了向中枢神经系统的有效递送;对酶促降解高度敏感,这损害了稳定性和治疗效果;以及非选择性结合,这降低了特异性并可能导致意外的脱靶效应。本综述系统地涵盖了先进的骨形态发生蛋白递送系统,如纳米颗粒、智能载体、基因治疗和基于外泌体的系统。水凝胶、支架和微球的局部递送方法也作为有前景的选择进行了讨论。体外研究表明骨形态发生蛋白是有效的,并且在体内神经胶质瘤模型中的应用也有证据证明骨形态发生蛋白的有效性。此外,新的临床试验揭示了对骨形态发生蛋白的安全性、耐受性和治疗效果的关注,特别是它们与化疗和免疫疗法的联合应用。通过个性化医学和CRISPR/Cas工程进一步优化了骨形态发生蛋白的特异性和治疗性能。然而,监管障碍和产品商业化是具有挑战性的问题。本综述强调需要新的方法和先进技术来应对与骨形态发生蛋白递送相关的挑战,旨在将基于骨形态发生蛋白的疗法确立为神经胶质瘤的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04f0/12136072/f0bb0398766f/IJN-20-7093-g0001.jpg

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