Whole-cell SELEX aptamer-functionalised poly(ethyleneglycol)-poly(ε-caprolactone) nanoparticles for enhanced targeted glioblastoma therapy.
Though there has been substantial advancement in the knowledge about tumour development and treatment in the past 40 years, the prognosis of brain glioblastoma is still very grim due to the difficulty of targeting drugs to glioblastoma cells. An active targeting delivery system helps increase intracellular drug delivery, which is promising for the treatment of glioblastoma. For an active targeting delivery system, targeting ligands are crucial for efficient intracellular drug delivery. Current methods include systematic evolution of ligands by exponential enrichment (SELEX), which has been utilised for selecting specific ligands with better targeting effects. The GMT8 aptamer was a short DNA sequence selected by SELEX that could specifically bind with U87 cells. In this study, nanoparticles functionalised with GMT8 aptamers (ApNP) were utilised for glioblastoma therapy. In vitro cell uptake and U87 tumour spheroid uptake demonstrated that nanoparticles functionalised with GMT8 aptamer significantly enhanced intracellular drug delivery and tumour spheroid penetration. Assays for cell apoptosis and growth inhibition of tumour spheroids identified docetaxel-loaded ApNP to significantly induce cell apoptosis and inhibit tumour spheroid growth. In vivo imaging of glioblastoma-bearing mice demonstrated that ApNP could target glioblastoma and accumulate at the tumour site, which was further verified by fluorescence imaging of brain slices. Pharmacodynamic results indicated that docetaxel-loaded ApNP significantly prolonged the median survival time of glioblastoma-bearing mice compared to NP, DTX and control. In conclusion, GMT8 aptamer-functionalised nanoparticles enhanced tumour penetration and targeted glioblastoma therapy, which is promising for the prognosis of brain glioblastoma.
Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Huile
H
Gao
Jun
J
Qian
Zhi
Z
Yang
Zhiqing
Z
Pang
Zhangjie
Z
Xi
Shijie
S
Cao
Yuchen
Y
Wang
Shuaiqi
S
Pan
Shuang
S
Zhang
Wei
W
Wang
Xinguo
X
Jiang
Qizhi
Q
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005909:Glioblastoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000378:metabolism*; D052156:SELEX Aptamer Technique / Q000379:methods*
D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols