99mTc-labeled keratin gold-nanoparticles in a nephron-like microfluidic chip for photo-thermal therapy applications

Biocompatible gold nanoparticles (AuNPs) are particularly interesting for photo-thermal therapy (PTT) of cancer treatment because of their ability to convert light into heating efficiently. Nevertheless, the random accumulation of AuNPs in tissues, mainly determined by their retention time in the bloodstream, is one of the main limiting factors for their use in PTT applications. For this reason, efficient targeting and monitoring of AuNPs in the selected tissues is of paramount importance. This manuscript reports on a new generation of 99mTc-labeled AuNPs coated with keratin (Ker-AuNPs) and their spatial localization investigated by nuclear imaging techniques on an animal-free model. The effective radiolabeling of Ker-AuNPs with 99mTc is achieved using the chelating agent diethylenetriaminepentaacetic acid (DTPA), resulting in the 99mTc-DTPA-Ker-AuNPs nanoconjugate. The 99mTc-DTPA-Ker-AuNPs display a radiochemical purity of 90.7% and excellent photo-thermal properties. In addition, the biocompatibility of the 99mTc-DTPA-Ker-AuNPs with healthy human embryonic kidney (HEK293T) cells is shown. A Lab-On-a-Chip (LoC) approach is used to localize and study the stability of 99mTc-DTPA-Ker-AuNPs under dynamic conditions. To this end, the nanoconjugates are injected into a polydimethylsiloxane microfluidic chip mimicking the renal filtering unit, the nephron, and monitored via radio-imaging and thermo-optical experiments. These detailed studies establish that DTPA-assisted 99mTc-labeled Ker-AuNPs are excellent candidates as biocompatible and non-invasive radiolabeled nanotherapeutic for PTT-based applications.