Abstract A82: Localized tumor delivery of radiosensitizers and chemotherapeutics using ‘INCeRT’ implants.

Abstract

Abstract In cancer therapy, effective delivery of the therapeutic plays a critical role in determining the success of the treatment planning system. In last decade, there is a major thrust in developing novel nanoparticles based delivery systems to improve the therapeutic benefits in cancer. An efficient delivery system should be able to target the diseased site with minimal systemic toxicity and a slow sustained release of the drug. Here, we have fabricated a nanoparticles based smart ‘INCeRT’ (Implantable Nanoplatform for Chemo-Radiation Therapy) implant for localized delivery of radiosensitizing nanoparticles/ drugs in prostate cancer in conjunction with brachytherapy. These implants are physically similar to the clinically used brachytherapy spacers but have the added capability of imaging and local drug delivery. We have fabricated INCeRT spacers with biocompatible and biodegradable polymer, PLGA (poly-(lactide-co-glycolide)) impregnated with nanoparticles encapsulating imaging probe (Cyanine 7.5) and chemotherapeutic drug, docetaxel (DTX). Using a similar approach, we have also fabricated PLGA spacers impregnated with high Z (atomic number) gold nanoparticles (Hi-Z-CuRE: High Z-Customizable Radiotherapy Enhancement) for effectively boosting the radiation dose locally. The morphology, composition and nanoparticle's distribution inside the spacers was studied by SEM (scanning electron microscopy) and EDS (Energy-dispersive X-ray spectroscopy). Further, preliminary in vivo imaging experiments with subcutaneous prostate cancer tumored mice implanted with INCeRT spacers showed a size dependent diffusion of nanoparticles from the spacers in the tumor matrix. Also, from in vivo therapeutic studies with these spacers showed a sustained and slow release of the DTX from the spacers and showed a better response in suppressing the tumor as opposed control mice with saline injections. Further experiments for studying the combined chemo-radiation therapy are underway. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. This work was supported partially by NSF-DGE-0965843, HHS/1U54CA151881 CORE1, 1R03 CA164645-01 and a seed grant from the BWH Biomedical Research Institute. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A82. Citation Format: Rajiv Kumar, Jodi E. Belz, Stacey Markovic, Houari Korideck, Wilfred F. Ngwa, Mark Niedre, Ross I. Berbeco, Robert Cormack, Mike G. Makrigiorgos, Srinivas Sridhar. Localized tumor delivery of radiosensitizers and chemotherapeutics using ‘INCeRT’ implants. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A82.