Purpose: Image‐guided radiation treatments routinely utilize radio‐opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be enhanced through simultaneous in‐situ delivery of radiosensitizers, contained within nanoparticles and nanoporous polymer matrices coating gold fiducial markers or spacers implanted in the tumor (BIS‐IGRT, Biological In‐Situ Image‐Guided Radiation Therapy). Methods and Materials: Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed controlled release of molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system, (Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating) and (ii) Poly(D,L‐lactic‐co‐glycolic acid) (PLGA) nanoparticles loaded with Coumarin‐6, a fluorescent model for a hydrophobic drug, in a chitosan matrix applied as gold fiducial coating. Measurements of temporal release kinetics in buffer and spatial release profiles in agarose were carried out using fluorescence spectroscopy. Results: For gold fiducials coated with Doxorubicin in PMMA matrix an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin‐6 loaded nanoparticles from chitosan film on gold fiducials showed that (63±10)% of NPs were released in twenty days, and after that, the release became slower and additional 37% of release was observed after additional twenty‐days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Conclusions: The results show that dosage and rate of release of these radiosenstizers can be precisely tailored to achieve the desired release profile for BIS‐IGRT.
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