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

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• 作者：Lei Song ; Yuan Guo ; Deborah Roebuck ; Chun Chen ; Min Yang ; Zhongqiang Yang ; Sreejesh Sreedharan ; Caroline Glover ; Jim A. Thomas ; Dongsheng Liu ; Shengrong Guo ; Rongjun Chen ; Dejian Zhou
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：August 26, 2015
• 年：2015
• 卷：7
• 期：33
• 页码：18707-18716
• 全文大小：507K
• ISSN：1944-8252

文摘

Over the past 10 years, polyvalent DNA鈥揼old nanoparticle (DNA鈥揋NP) 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鈥揋NP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA鈥揋NP 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.