DNA Origami‐Enabled Engineering of Ligand–Drug Conjugates for Targeted Drug Delivery

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 16; no. 16; pp. e1904857 - n/a
• Main Authors: Ge, Zhilei, Guo, Linjie, Wu, Guangqi, Li, Jiang, Sun, Yunlong, Hou, Yingqin, Shi, Jiye, Song, Shiping, Wang, Lihua, Fan, Chunhai, Lu, Hua, Li, Qian
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2020
• Subjects: Antibodies; Antigens; Biocompatibility; Cancer; Conjugates; Conjugation; DNA nanostructures; Doxorubicin; drug carriers; Drug delivery systems; drug‐to‐ligand ratio; framework nucleic acids; Ligands; Nanocomposites; Nanotechnology; Payloads; Prostate; System effectiveness; targeting ligands; drug carriers; DNA nanostructures; framework nucleic acids; drug-to-ligand ratio; targeting ligands
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201904857

Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligand‐modified DNA origami nanostructure (DON) as an antibody–drug conjugate (ADC)‐like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2‐[3‐(1,3‐dicarboxy propyl)‐ureido] pentanedioic acid (DUPA) against prostate‐specific membrane antigen (PSMA), to serve as the antibody for drug conjugation in ADC. Doxorubicin (Dox) is then loaded to DON through intercalation to dsDNA. This platform features in spatially controllable organization of targeting ligands and high drug loading capacity. With this nanocomposite, selective delivery of Dox to the PSMA+ cancer cell line LNCaP is readily achieved. The consequent therapeutic efficacy is critically dependent on the numbers of targeting ligand assembled on DON. This target‐specific and biocompatible drug delivery platform with high maximum tolerated doses shows immense potential for developing novel nanomedicine. This DNA‐based, DNA origami nanostructure (DON)‐enabled, cell‐selective, and biocompatible drug delivery platform with high “drug/ligand ratio” shows immense potential as an efficient drug carrier for developing novel nanomedicine with high pharmacokinetics and therapeutic index.