(600b) Enhanced Penetration into Drug-Resistant Tumor Tissue and Cytotoxicity of Doxorubicin Loaded on Gold Nanoparticles | AIChE

(600b) Enhanced Penetration into Drug-Resistant Tumor Tissue and Cytotoxicity of Doxorubicin Loaded on Gold Nanoparticles

Authors 

Kim, B. - Presenter, University of Massachusetts
Forbes, N. S. - Presenter, University of Massachusetts Amherst
Han, G. - Presenter, University of Massachusetts
Rotello, V. - Presenter, University of Massachusetts


Drug penetration into tumor tissue and multi-drug resistance related with P-glycoprotein limit the efficiency of chemotherapy for many types of cancers. Controlled release from drug carriers is also an important issue to expose cells to the drugs at a cytotoxic concentration for a certain period minimizing adverse effects. To address these problems, monolayer protected gold nanoparticles were prepared as a drug carrier. The monolayer is comprised of tetra(ethylene glycol)lyated amine ligand and thiolated doxorubicin. The amine group was designed to provide cationic surface to enhance the cellular uptake and the release of thiolated drug was mediated by the cytoplasmic glutathione. Because of the fluorescence quenching by gold nanoparticles, amount of free doxorubicin released from the nanoparticles was able to be quantified by measuring fluorescent excitation at 650nm (long pass). Penetration and cytotoxicity of gold nanoparticle-conjugated doxorubicin into tumor tissue consisting of drug sensitive MCF-7 and resistant NCI/ADR cells were determined with epi-fluorescence microscopy and outgrowth assay and compared with the results from the treatments of doxorubicin alone. While doxorubicin penetrated deep into the center of the cylindroid of MCF-7 cells, the concentration of doxorubicin was sharply decreased from the peripheral region toward the center and significantly lower around the center of the cylindroids of NCI/ADR cells. When the cylindroids were treated with gold nanoparticle-conjugated doxorubicin, the drug penetration took longer for the cylindroids of both types of cells but the penetration depth significantly increased for the cylindroids of NCI/ADR cells. The cytotoxicity of doxorubicin loaded on gold nanoparticles significantly increased for the cylindroid of NCI/ADR cells due to the prolonged release in the cytoplasm from nanoparticles. In this study, we have shown characteristics of penetration of nanoparticle and enhanced penetration and cytotoxicity of gold nanoparticle-conjugated doxorubicin to the tissue consisting of the drug-resistant cells.