title: Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins.
abstract: Although the delivery of biologically functional protein(s) into mammalian cells could be of tremendous value to biomedical research, the development of such technology has been hindered by the lack of a safe and effective delivery method. Here, we present a simple, efficient, and versatile gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system, with nanoblock-like properties, that allows any recombinant protein to be loaded without additional modifications and delivered into mammalian living systems. AuNP-Apt-based protein delivery system was able to deliver various proteins into variety of cell types in vitro without showing cytotoxicity. This AuNP-Apt system was also effective for the local and systemic targeted delivery of proteins in vivo. A local injection of the AuNP-Apt loaded with the apoptosis-inducing BIM protein efficiently inhibited the growth of xenograft tumors in mice. Furthermore, an intravenous injection of AuNP-Apt loaded with both epidermal growth factor (EGF) and BIM resulted in the targeted delivery of BIM into a xenograft tumor derived from EGF receptor-overexpressing cancer cells with no detectable systemic toxicity. Our findings show that this system can serve as an innovative platform for the development of protein-based biomedical applications.
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Ryou
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yeom
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pharmacy, CHA University, Seongnam 463-836, Republic of Korea.
authors.forename: Miae
authors.initials: M
authors.lastname: Won
authors.affiliation: Department of Manufacturing Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jin-Sik
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Boeun
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Physics, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Maeng-Je
authors.initials: MJ
authors.lastname: Seong
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: jeehyeon@cau.ac.kr.
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: kangseok@cau.ac.kr.
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006046:Gold; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; D052157:Aptamers, Nucleotide; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C000606778:Bcl2l11 protein, rat; D004337:Drug Carriers; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D006046:Gold
keywords: Aptamer; Gold nanoparticle; Protein delivery; Targeted delivery