Poster Sessions

MOLBIO/BIOCHEM/BIOPHYS-4

Haitao Wu

H. Wu, K. Brimacombe, H. Sarin, B. Xu, C. Wilson, M. Hall, G. Griffiths

Synthesis of a Bifunctional PAMAM Dendrimer Nanoparticle Bearing Both a Chemotherapy Drug for Brain Tumor Treatment Studies and an MRI Agent for Tracking Purposes

Nanoparticle drug delivery systems have been found to improve drug efficacy and target specificity through an increased drug-at-tumor half-life, owing to the enhanced permeability and retention (EPR) effect. Doxorubicin, delivered by a dendrimer vehicle and attached via a pH-sensitive hydrazone bond, was found capable of selective release and anti-tumor activity. Meanwhile, a gadolinium-bearing MR visible dendrimer nanoparticle provides a convenient tool for in vivo monitoring of drug biodistribution. A 5th generation (G5) polyamidoamine (PAMAM) dendrimer therapeutic/diagnostic bifunctional agent was synthesized with terminally conjugated Gd-DTPA moieties for magnetic resonance imaging and doxorubicin for prolonged and target-specific drug release. The Gd-G5-doxorubicin dendrimer was determined to have a total mass of 84.7 kDa with approximately 10 doxorubicin molecules and 61 Gd atoms per unit of dendrimer. Confocal microscopy showed conjugate accumulations in cancer cells and doxorubicin presence in the nucleus. This new Gd-G5 dendrimer contrast agent/drug delivery system may be a promising approach for the transvascular drug delivery of small chemotherapy drugs into malignant brain tumors with concomitant diagnostic tracking.