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A Camptothecin‐Grafted DNA Tetrahedron as a Precise Nanomedicine to Inhibit Tumor Growth
Author(s) -
Zhang Jiao,
Guo Yuanyuan,
Ding Fei,
Pan Gaifang,
Zhu Xinyuan,
Zhang Chuan
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201907380
Subject(s) - camptothecin , nanomedicine , dna , combinatorial chemistry , chemistry , aqueous solution , drug , bioconjugation , drug delivery , biophysics , conjugate , in vivo , nanotechnology , materials science , nanoparticle , biochemistry , pharmacology , organic chemistry , biology , mathematical analysis , mathematics , microbiology and biotechnology
Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic form before administration. Based on the excellent hydrophilicity and programmability of DNA, now, a general strategy to construct a precise drug‐containing DNA framework for cancer treatment is reported. In this novel drug delivery system, carbonethyl bromide‐modified camptothecin (CPT) is employed to directly react with phosphorothioate (PS) modified DNAs, resulting in the formation of chemotherapeutics‐grafted DNAs with a responsive disulfide linkage. By tuning the number and site of PS modifications on DNA strands, hydrophilicity of the obtained DNA‐drug conjugates (DDCs) can be regulated to retain their aqueous solubility and capability of molecular recognition. Subsequently, programmable DNA nanotechnology enables the self‐assembly of a precise drug‐containing tetrahedral framework with stimuli‐responsive feature and enhanced antitumor efficacy both in vitro and in vivo.