A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo

Abstract

Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.

Targeting nucleolin to obstruct vasculature feeding with an intelligent DNA nanorobot

“…E, Representative pictures of the tumours from the MDA‐MB231 tumour‐bearing mice after treatment with saline and nanorobot‐Th. Adapted with permission from Reference Li et al . Copyright 2018 Nature Publishing Group…”

“…Developed in 2006, DNA origami turns out a handy design technique to create arbitrary shapes with a long single‐stranded DNA serving as a scaffold and hundreds of ‘staple’ strands maintaining the scaffold in position. With the origami technique, a 90 × 60 nm rectangular sheet was constructed (Figure A). Through thrombin‐DNA conjugation and DNA‐DNA hybridization, ~4 thrombin payloads on the surface of each DNA sheet were assembled.…”

“…Because of its indiscriminative effects and short circulation half‐life, thrombin had been removed from cancer treatment before. With this DNA nanorobot, to precisely deliver thrombin solely to tumour sites in a highly controlled autonomous manner was managed to maximize its biostability and drug efficacy as well as minimize its toxicity . The approach in principle was applicable to deliver a wide range of drug candidates that had been previously excluded from clinical use because of unwanted stability issues or side effects.…”

“…Biosafety assessments of the DNA nanorobot system had been carried out . In non‐tumour‐bearing healthy mice, no significant changes were observed in blood coagulation parameters after treatment with nanorobot‐Th.…”

A Review on Dna Nanobots – A New Technique for Cancer Treatment

“…Although these bots were built without any particular purpose, they have a very good application in cancer treatment. Scientists have lately built up nanobots that deliver thrombin, an enzyme which clots the blood that goes to the tumor and thereby destroys the tumor [47][48][49]. This trial has given hope that nanobots are safe enough and can be used as an effective cancer treatment method.…”