Depot system for controlled release of gold nanoparticles with precise intratumoral placement by permanent brachytherapy seed implantation (PSI) techniques

We report the design of a nanoparticle depot (NPD) system for local delivery of gold nanoparticles (AuNP) that facilitates their controlled release and is implantable into tumors by permanent seed implantation (PSI) brachytherapy techniques. Various sizes (5, 15, 30, and 50 nm) of polyethylene glycol (PEG) coated AuNP and concentrations (6%, 8%, and 10% w/v) of calcium alginate used to form the NPD were studied. AuNP release rate, diffusion characteristics and spatial distribution were characterized in a tissue equivalent phantom model, and in a breast cancer tumor xenograft model and compared to a Fickian diffusion computational model, to identify the optimal NPD composition. In phantoms, 5 nm and 15 nm AuNP were released more rapidly than 30 nm or 50 nm AuNP but when implanted into tumor xenografts, AuNP exhibited slower release from NPD. Controlled prolonged release of AuNP was observed in tumor tissue over durations which were dependent on AuNP size. Maximum release and distribution in tumors were achieved using 5 nm AuNP incorporated into the NPD. These results demonstrate the potential for the NPD as an effective local delivery system for AuNP-based therapies.

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