The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma

Xu, Haoyue1; Zhang, Yongkang1; Li, Linfeng1; Ren, Yanhong1; Qian, Feng1; Wang, Lansheng1; Ma, Hongwei1; Quan, Ankang1; Liu, Hongmei1,3; Yu, Rutong1,2

2023-12-31

10.1080/10717544.2022.2152911

DRUG DELIVERY   Impact Factor & Quartile

1071-7544

1521-0464

Temozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved.

Glioma drug-resistance siMGMT P(TMZ)n

SCI

English

Corresponding

[82072796] ; [BE2020642] ; [KYCX21_2657] ; [KYCX22_2950] ; [M2020081]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000904946100001

TAYLOR & FRANCIS LTD

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Xuzhou Med Univ, Inst Nervous Syst Dis, Xuzhou, Peoples R China
2.Xuzhou Med Univ, Dept Neurosurg, Affiliated Hosp, Xuzhou, Peoples R China
3.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen, Peoples R China

Xu, Haoyue,Zhang, Yongkang,Li, Linfeng,et al. The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma[J]. DRUG DELIVERY,2023,30(1).

Xu, Haoyue.,Zhang, Yongkang.,Li, Linfeng.,Ren, Yanhong.,Qian, Feng.,...&Yu, Rutong.(2023).The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma.DRUG DELIVERY,30(1).

Xu, Haoyue,et al."The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma".DRUG DELIVERY 30.1(2023).