Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea.
J Mater Chem B. 2024 Sep 25;12(37):9335-9344. doi: 10.1039/d4tb00631c.
Glioblastoma (GBM) is one of the most common and fatal primary brain tumors, with a 5-year survival rate of 7.2%. The standard treatment for GBM involves surgical resection followed by chemoradiotherapy, and temozolomide (TMZ) is currently the only approved chemotherapeutic agent for the treatment of GBM. However, hydrolytic instability and insufficient drug accumulation are major challenges that limit the effectiveness of TMZ chemotherapy. To overcome these limitations, we have developed a drug delivery platform utilizing porous silicon nanoparticles (pSiNPs) to improve the stability and blood-brain barrier penetration of TMZ. The pSiNPs are synthesized electrochemical etching and functionalized with octadecane. The octadecyl-modified pSiNP (pSiNP-C) demonstrates the superiority of loading efficiency, stability, and brain accumulation of TMZ. Treatment of intracranial tumor-bearing mice with TMZ-loaded pSiNP-C results in a decreased tumor burden and a corresponding increase in survival compared with equivalent free-drug dosing. Furthermore, the mice treated with TMZ-loaded nanoparticles do not exhibit toxicity, thus underscoring the preclinical potential of the pSiNP-based platform for the delivery of therapeutic agents to gliomas.
胶质母细胞瘤（GBM）是最常见和致命的原发性脑肿瘤之一，5 年生存率为 7.2%。GBM 的标准治疗包括手术切除后进行放化疗，替莫唑胺（TMZ）是目前唯一被批准用于治疗 GBM 的化疗药物。然而，水解不稳定性和药物蓄积不足是限制 TMZ 化疗效果的主要挑战。为了克服这些限制，我们开发了一种利用多孔硅纳米粒子（pSiNPs）的药物递送平台，以提高 TMZ 的稳定性和血脑屏障穿透性。pSiNPs 通过电化学蚀刻合成，并与十八烷功能化。十八烷基修饰的 pSiNP（pSiNP-C）在 TMZ 的载药效率、稳定性和脑内蓄积方面表现出优越性。用载 TMZ 的 pSiNP-C 治疗颅内荷瘤小鼠，与等效的游离药物剂量相比，肿瘤负担减少，生存时间相应延长。此外，接受载药纳米粒子治疗的小鼠没有表现出毒性，这突出了基于 pSiNP 的平台在将治疗剂递送到神经胶质瘤方面的临床前潜力。
