A gated material as immunosensor for in-tissue detection of IDH1-R132H mutation in gliomas

SENSORS AND ACTUATORS B-CHEMICAL

卷:345

Article

Pla, Luis^1,2,3  Sancenon, Felix^1,2,3,4,5  Carmen Martinez-Bisbal, M.^1,2,3,4,6  Prat-Acin, Ricardo^3,7,8  Galeano-Senabre, Inmaculada^3,7  Botello-Marabotto, Marina^2,3  Palanca-Suela, Sarai⁹  Aznar, Elena^1,2,3,4,5  Santiago-Felipe, Sara^1,2,3  Martinez-Manez, Ramon^1,2,3,4,5 

[1] CIBER Bioingn Biomat & Nanomed CIBER BBN, Valencia, Spain

[2] Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Camino Vera S-N, Valencia 46022, Spain

[3] Univ Politecn Valencia, Inst Invest Sanitaria La Fe IISLAFE, Unidad Mixta Invest Nanomed & Sensores, Valencia, Spain

[4] Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain

[5] Univ Politecn Valencia, Dept Quim, Valencia, Spain

[6] Univ Politecn Valencia, Dept Quim Fis, Valencia, Spain

[7] Hosp Univ & Politecn La Fe, Serv Neurocirugia, Valencia, Spain

[8] Univ Valencia, Dept Cirugia, Valencia, Spain

[9] Hosp Univ & Politecn La Fe, Serv Anal Clin, Unidad Biol Mol, Valencia, Spain

关键词: Glioblastoma;    Nanoporous anodic alumina;    Gated material;    Antibody;    IDH1;   

DOI  :  10.1016/j.snb.2021.130406

来源: Elsevier

【 摘 要 】

A nanodevice consisted on nanoporous anodic alumina (NAA) supports functionalized with specific and selective antibody-based gatekeepers for the detection of IDH1-R132H mutant enzyme is here reported. Molecular profile and tissue mutations of the tumours (such as IDH1/IDH2 mutations in gliomas) are a great source of information that already make a difference in terms of prognosis and prediction of response to combined therapy. However, standardized methodologies to determine this mutation are time-consuming and cannot provide information before or during surgical intervention, which significantly limits their utility in terms of intraoperative decisionmaking. To solve this limitation, our sensing system, in the presence of the target IDH1-R132H mutant enzyme triggers the delivery of a fluorescent reporter from the antibody-capped NAA that is easily detected using a standard fluorimeter in less than 1 h. Good capabilities of the sensor in terms of sensitivity (limit of detection as low as 0.01 ng/mL) and selectivity are determined. The biosensor is validated in seventeen human glioma tissue samples, also analysed by standardized methodologies, showing significant differences between IDH1 wild-type and IDH1-R132H mutant gliomas (p < 0.01) with high sensitivity, specificity and accuracy (87.5/88.9/88.2) for IDH1-R132H mutational status classification in human glioma tissues. This new detection system might play an important role in surgical interventions, anticipating mutational status information in gliomas and supporting thus decision making and patient survival.

【 授权许可】

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