DNA Origami-Enabled Engineering of Ligand-Drug Conjugates for Targeted Drug Delivery.
Zhilei GeLinjie GuoGuangqi WuJiang LiYunlong SunYingqin HouJiye ShiShiping SongLihua WangChunhai FanHua LuQian LiPublished in: Small (Weinheim an der Bergstrasse, Germany) (2020)
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.
Keyphrases
- cancer therapy
- drug delivery
- drug release
- prostate cancer
- pet ct
- circulating tumor
- cell free
- induced apoptosis
- pet imaging
- high throughput
- adverse drug
- single molecule
- benign prostatic hyperplasia
- papillary thyroid
- diffusion weighted
- emergency department
- signaling pathway
- risk assessment
- high resolution
- young adults
- endoplasmic reticulum stress
- quantum dots
- single cell