Terminal PEGylated DNA–Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

• Published in: ACS applied materials & interfaces 2015-08, Vol.7 (33), p.18707-18716
• Main Authors: Song, Lei, Guo, Yuan, Roebuck, Deborah, Chen, Chun, Yang, Min, Yang, Zhongqiang, Sreedharan, Sreejesh, Glover, Caroline, Thomas, Jim A, Liu, Dongsheng, Guo, Shengrong, Chen, Rongjun, Zhou, Dejian
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - toxicity; Cell Survival - drug effects; Coordination Complexes - chemistry; Coordination Complexes - metabolism; Deoxyribonuclease I - chemistry; Deoxyribonuclease I - metabolism; DNA - chemistry; DNA - metabolism; Doxorubicin - chemistry; Doxorubicin - toxicity; Drug Carriers - chemistry; Dynamic Light Scattering; Gold - chemistry; HeLa Cells; Humans; Intercalating Agents - chemistry; Intercalating Agents - metabolism; Metal Nanoparticles - chemistry; Microscopy, Confocal; Polyethylene Glycols - chemistry; Propidium - chemistry; Propidium - metabolism; Ruthenium - chemistry
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.5b05228

Over the past 10 years, polyvalent DNA–gold nanoparticle (DNA–GNP) conjugate has been demonstrated as an efficient, universal nanocarrier for drug and gene delivery with high uptake by over 50 different types of primary and cancer cell lines. A barrier limiting its in vivo effectiveness is limited resistance to nuclease degradation and nonspecific interaction with blood serum contents. Herein we show that terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA–GNP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA–GNP conjugate still retains a high cell uptake property, making it an attractive intracellular delivery nanocarrier for DNA binding reagents. We show that it can be used for successful intracellular delivery of doxorubicin, a widely used clinical cancer chemotherapeutic drug. Moreover, it can be used for efficient delivery of some cell-membrane-impermeable reagents such as propidium iodide (a DNA intercalating fluorescent dye currently limited to the use of staining dead cells only) and a diruthenium complex (a DNA groove binder), for successful staining of live cells.