Implantable Nanoparticles Doped Brachytherapy Spacers for Synergistic Combinatorial Chemo-radiation Therapy in Prostate Cancer

Abstract

We describe efforts towards developing nanoparticle based platforms for localized delivery of therapeutics in conjunction with radiation therapy in prostate cancer. The use of nanoparticles in fabricating brachytherapy spacers provides a sustained release depot of drug delivering chemotherapeutic drugs at target site locally, resulting in local radio-sensitization of prostate with the use of lower radiation doses and thereby leading to less rectal toxicity. æWe have synthesized mesoporous silica based nanoparticles encapsulating radiosensitizing anti-cancer drug, Docetaxel (DTX) and conjugated with a near infra-red (NIR) fluorophore Cy 7.5 (for optical tracking of the nanoparticles) via the micro-emulsion method. Silica nanoparticles were characterized by DLS, TEM, absorbance and photoluminescence studies. The encapsulation efficiency of DTX in nanoparticles was characterized using high performance liquid chromatography. The nanoparticles encapsulating DTX showed a sustained release of the drug in buffer. In vitro cytotoxicity studies with PC3 cells showed the biocompatibility of blank silica nanoparticles whereas an efficient therapeutic response with DTX encapsulated nanoparticles. Further, these nanoparticles were incorporated into a polymer matrix of PLGA (poly (lactide-co-glycolide)) and formulated into small cylinders of standard brachytherapy spacerÍs length. These polymeric spacers were characterized by SEM for the nanoparticles distribution within the polymeric matrix. The release kinetics studies were performed to estimate a sustained release of the drug from the nanoparticles entrapped in the polymer matrix. This combinatorial approach is expected to enhance the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. Work supported by NSF-DGE- 0965843, HHS/1U54CA151881 CORE1 and ARMY/ W81XWH-12-1-0154.