In a study published inTrends in Biotechnology on Dec. 20, a research team led by Prof. CAI Lintao and Prof. MA Teng from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, along with their collaborators, developed a photosynthetic bacteria–red blood cell (RBC) hybrid microrobot (PR-robot), which is capable of autonomous hypoxia sensing and exhibits responsiveness to ultrasound.

Micro-/nano-biorobots exhibit precisely controllable behavior, diverse functionalities, and excellent biocompatibility, making them ideal tools for precision medicine and complex biological tasks. However, effectively controlling their motion and functions continues to present a challenge.

Ultrasound provides strong penetration in deep biological tissues with non-invasiveness, remote precise actuation, and excellent biosafety. Consequently, ultrasound-driven micro- and nanobiorobots hold considerable promise for advanced biomedical applications.

In this study, researchers developed the PR-robot through Michael addition conjugation.By utilizing the unique hypoxia-sensing capabilities of photosynthetic bacteria and their secretion of bacterial chlorophyll, the PR-robot was equipped with tumor-targeting and photothermal therapy functionalities.More importantly, the biconcave disc structure of RBCs enhances acoustic impedance, conferring ultrasound responsiveness property. As a result, the PR-robot integrates tumor-targeting and photothermal therapy with ultrasound-driven propulsion.

Experimental results showed that ultrasonic tweezers can cluster PR-robots into bioswarms and precisely guide them along predefined trajectories, even moving against fluid flow.

Furthermore, researchers confirmed that these bio-swarms can be guided to penetrate biological barriers, achieving deep tissue permeation. As the PR-robots accumulate, they induce extensive tumor-specific thrombosis, which synergistically enhances the efficacy of photothermal therapy.

This work introduces a novel technological strategy and design concept for ultrasound-mediated deep drug delivery and treatment of related diseases.

Ultrasound-driven bacteria–red blood cell microrobots for bioswarms manipulation and deep penetration in cancer therapy. (Image by SIAT) 

Media Contact: LU Qun

Email: qun.lu@siat.ac.cn

Download the attachment：

Programmable ultrasound-mediated swarms manipulation of bacteria–red blood cell microrobots for tumor-specific thrombosis and robust photothermal therapy