(459a) Molecular Recognition and In Vivo Detection of Temozolomide and 5-Aminoimidazole-4-Carboxamide for Glioblastoma Using Fluorescent Nanosensors

The efficacy of chemotherapeutics such as temozolomide (TMZ) and its metabolic product 5-aminoimidazole-4-carboxamide (AIC) is often affected by the timing, quantity and frequency of dosages. There is strong interest in facilitating the ability to monitor efficacy in individual patients for specific subtypes of cancer. Real-time, dynamic measures of potency may also supplement or in some cases replace reliance on bio-imaging. Towards this end, in this work we develop new, synthetic molecular recognition sites for TMZ, and its decomposition product AIC, grafting them onto near infrared fluorescent nanoparticles capable of forming optode or other biosensor interfaces to monitor drug efficacy in real-time. 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. In both solution phase and hydrogel form, the sensors exhibit a fluorescence response to TMZ with a detection limit of 30 M. Furthermore, U-87 cells exhibit no changes in viability for 7 days in contact with the hydrogel. The sensors were used to track the progression of glioblastoma death following TMZ administration. In addition, the sensors were able to monitor in vivo AIC and TMZ dynamics in SKH-1E mice. These results enable real-time detection of chemotherapeutic concentration and metabolism at the cellular and subcellular levels, with potential to increase the efficacy of cancer treatments.