Abstract No. 419 - CT-guided intra-tumoral injection of gold-coated Clostridium novyi-NT spores for bacteriolytic therapy in solid tumors

Abstract

Bacteriolytic therapy using anaerobic bacteria is considered as a promising approach for the treatment of solid tumors. To improve therapeutic efficacy while potentially reducing toxicity, we demonstrate an approach to label Clostridium novyi-NT (C. novyi-NT) spores with branched gold nanoparticles (BGNP) thus permitting intra-procedural X-ray CT visualization of spore delivery to solid tumors upon intra-tumoral injection. C. Novyi-NT spores were kindly provided by BioMed Valley Discoveries (Kansas City, MO, USA). BGNP were synthesized in an aqueous solution of sodium cholate and then the BGNP were modified with 4-mercaptobenzoic acid to render negatively charge. BGNP-coated spores were prepared using a simple electrostatic deposition method. In vitro phantom and in vivo (PC-3 human prostate cancer mice model) CT studies were performed using a micro-CT imaging system (NanoPET/CT®, Mediso Ltd-Bioscan Inc., Hungary-US). Successful preparation of BGNP-coated C. Novyi-NT spores was confirmed by various physico-chemical characterization methods. In the PC3 mouse model, BGNP-coated spores were locally injected into the hypoxic center of each tumor guided with CT confirmation of intra-tumoral delivery. The therapeutic efficacy of these CT-guided infused BGNP-coated spores demonstrated in immunohistochemical analyses such as H&E and TUNEL staining. The infused BGNP-coated spores exhibited strong therapeutic efficacy consistent with that observed for native spores suggesting that the innate anti-tumoral function was preserved. Our BGNP-coating on the C. Novyi-NT spores have the potential to not only facilitate CT image-guided bacteriolytic procedures but also to serve as a novel BGNP-mediated combinational therapeutic delivery platform.