(28f) Dynamics Monitoring of Temozolomide and 5-Aminoimidazole-4-Carboxamide for Glioblastoma Using Fluorescent Nanosensors

The efficacy of chemotherapeutics is often affected by the timing, quantity and frequency of dosages. Real-time, dynamic measures of potency may supplement or in some cases replace reliance on bio-imaging. Towards this end, in this work we develop synthetic molecular recognition sites for temozolomide (TMZ), and its decomposition product 5-aminoimidazole-4-carboxamide (AIC), grafting them onto fluorescent nanoparticles capable of forming optode or other biosensor interfaces to monitor drug efficacy in real-time. Near-infrared fluorescent single-walled carbon nanotubes, wrapped using specific DNA oligonucleotides, are encapsulated within biocompatible, poly(ethylene glycol) diacrylate hydrogels and enable the selective recognition of an anti-cancer drug, TMZ, on U-87 MG human glioblastoma cells. The sensors exhibit a fluorescence response to TMZ with a detection limit of 30 mM and used to track the progression of glioblastoma death following TMZ administration. For in vivo demonstration, the sensors were able to monitor TMZ dynamics and flux in SKH-1E mice. In fetal pig brain, deeply implanted sensors detected AIC dynamics by employing wavelength-induced frequency filtering technique. These results enable real-time detection of chemotherapeutic concentration and metabolism in vivo with potential to increase the efficacy of cancer treatments.