Li CH(1), Lv WY(1), Yan Y(2), Yang FF(2), Zhen SJ(2), Huang CZ(1). Author information:
(1)Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest
University), Ministry of Education, College of Pharmaceutical Sciences,
Southwest University, Chongqing 400715, P. R. China.
(2)Key Laboratory of Luminescent and Real-Time Analytical System (Southwest
University), Chongqing Science and Technology Bureau, College of Chemistry and
Chemical Engineering, Southwest University, Chongqing 400715, P. R. China.
Precise drug delivery holds great promise in cancer treatment but still faces challenges in controllable drug release in tumor cells specifically. Herein, a nucleolin-targeted and telomerase-responsive DNA nanotube for drug release was developed. First, a DNA nanosheet with four capture strands on its surface was prepared, which could bind and load ricin A chain (RTA). The RTA-loaded nanosheet was further converted into a DNA nanotube with a high Förster resonance energy transfer (FRET) efficiency in the presence of a Cy3-modified DNA fastener by hybridizing with the Cy5-modified DNA and another DNA-containing telomerase primer sequence along the long sides. Moreover, the aptamer of nucleolin was assembled on the DNA nanotube by combining with the hybrid chain at the terminal. The aptamer-functionalized and RTA-loaded DNA nanotube displayed enhanced tumor permeability and precise drug release in response to the telomerase in tumor cells, following the change of the FRET signal and RTA-induced cell death. Moreover, the DNA nanotube was applied successfully in vivo, and there was an obvious inhibition of tumor growth on xenograft-bearing mice following systemic administration, indicating that the constructed DNA nanotube represents a promising platform for precise RTA delivery in target cancer therapy.
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