title: Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier.
abstract: It is challenging to design rolling circle amplification (RCA) for tumor-selective delivery of drugs. Here, we devise a doxorubicin nanocarrier composed of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products, designed to contain tandem repeats of short hairpin DNA, employ the repeated sequences complementary to both DNA conjugates, and thus RCA products/cholesterol-DNA/folate-DNA complexes, generated via sequential base pairing processes, acquire the amphiphilic properties that facilitate self-assembly into the highly condensed nanoparticles (RCA nanoparticles). Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity, release drugs to the environment with the aid of acidity and show selective cytotoxicity to cancer cells. Particularly, the condensed structures enable RCA nanoparticles to be resistant to nucleases in the blood. These results show that RCA nanoparticles have great potential as a doxorubicin carrier for targeted cancer therapy, and furthermore, our strategy provides an alternative tool to exploit RCA techniques on drug delivery systems.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , 39-1 Hawolgok-dong, Seongbuk-Gu, Seoul 136-791, South Korea.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , 39-1 Hawolgok-dong, Seongbuk-Gu, Seoul 136-791, South Korea.
authors.forename: Mihue
authors.initials: M
authors.lastname: Jang
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , 39-1 Hawolgok-dong, Seongbuk-Gu, Seoul 136-791, South Korea.
authors.forename: Young-Je
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , 39-1 Hawolgok-dong, Seongbuk-Gu, Seoul 136-791, South Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Ahn
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D015195:Drug Design; D004355:Drug Stability; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D021141:Nucleic Acid Amplification Techniques
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D004247:DNA; D005492:Folic Acid; D002784:Cholesterol