Use of surface-modified porous silicon nanoparticles to deliver temozolomide with enhanced pharmacokinetic and therapeutic efficacy for intracranial glioblastoma in mice

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 o...

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Veröffentlicht in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-09, Vol.12 (37), p.9335-9344
Hauptverfasser: Shin, Seulgi, Jo, Hyejung, Agura, Tomoyo, Jeong, Seoyoun, Ahn, Hyovin, Kim, Yejin, Kang, Jae Seung
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Sprache:eng
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Zusammenfassung: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 via electrochemical etching and functionalized with octadecane. The octadecyl-modified pSiNP (pSiNP-C 18 ) demonstrates the superiority of loading efficiency, in vivo stability, and brain accumulation of TMZ. Treatment of intracranial tumor-bearing mice with TMZ-loaded pSiNP-C 18 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 in vivo toxicity, thus underscoring the preclinical potential of the pSiNP-based platform for the delivery of therapeutic agents to gliomas. Octadecylated pSiNPs efficiently deliver TMZ to the brain, enhancing its accumulation and anticancer effects, resulting in extended survival in glioma-bearing mice. It highlights its potential as a promising drug delivery platform for the brain.
ISSN:2050-750X
2050-7518
2050-7518
DOI:10.1039/d4tb00631c