“Nano couriers” achieve remote and accurate delivery of medicines through EMS

In the Hollywood movie “The Amazing Journey”, in order to treat the patient, the surgeon can shrink to one in a million and enter the human body to perform vascular surgery.

Nowadays, science fiction shines into reality, with the advent of the intelligent era, micro-nano robots that can perform tasks at the microscopic scale have attracted widespread attention because of their application in drug delivery, minimally invasive surgery, medical diagnosis, and treatment.

On February 23, Beijing time, a study published in the international academic journal Science Advances introduced a dual-engine, adaptive yeast micro-nano biorobot, which can penetrate multiple physiological barriers of the human body through the switching of biological enzymes and macrophage engines (EMS) like a “nano courier”, and achieve precise delivery of drugs to remote inflammatory lesions.

Screenshot of the paper

Cai Lintao, Associate Professor Pan Hong and Dr. Zheng Mingbin of the Nanomedicine and Technology Research Center of the Institute of Advanced Technology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences are the corresponding authors, and Zhang Baozhen, a doctoral student at the University of Chinese Academy of Sciences, is the first author; Shenzhen Advanced Institute is the first unit of thesis.

A micro-nano robot with “dual engines”

Micro-nano biorobots with self-propelled and navigation capabilities have attracted widespread attention because they can reach microscopic areas that are difficult to reach with existing medical devices, and are expected to realize precise diagnosis and treatment of diseases and revolutionize traditional medicine.

However, due to the multiple physiological barriers in the human body, it is still challenging to develop micro-nano biorobots that can adapt to changes in the microenvironment and deliver drugs to remote lesions accurately. Not only that, micro-nano biorobots must have ultra-high safety in order to be used in the human environment.

Micro-nano biorobots driven by biological enzymes use biocompatible substrates (such as glucose and urea) in vivo as fuel, and have broad application prospects in the field of drug delivery.

“Among them, yeast microcapsules are cell wall components of edible yeast probiotics, which are natural, hollow, porous microspheres that can be loaded with a variety of nanomedicines and can target macrophages, which aroused our interest.” Pan Hong, co-corresponding author of the paper, introduced that macrophages with inflammatory chemotaxis are also a natural cell engine.

“We found that yeast microcapsules can be engulfed by macrophages in the gut when taken orally, and the gradient of glucose concentration naturally stored in the intestine suggests that we can use cascades to drive robot movements.”

Further, using yeast microcapsules as active materials, the research team prepared yeast micro-nano biorobots (TBY-robots) with asymmetric structure by coupling glucose oxidase and catalase to the surface of yeast microcapsules wrapped in nanomedicines.

Greatly reduces the inflammatory response

Verification shows that after oral administration, TBY-robot can use the natural glucose concentration gradient in the intestine to penetrate the mucus barrier, cross the intestinal epithelial barrier through intestinal microfold cells, and switch to the macrophage engine in the Pear’s node on its own, and then use the inflammatory chemotaxis of macrophages to accurately deliver drugs to remote inflammatory sites through lymphatic circulation and blood circulation.

Yeast micro-nano biorobot realizes remote and precise delivery of drugs to inflammatory lesions through EMS Source: Photo provided by the scientific research team

In short, TBY-robots are like “nano couriers”, and Pear’s knots are similar to “transit stations”, switching between different means of transportation to accurately deliver drugs to the inflammatory area.

Researcher Cai Lintao, the corresponding author of the paper, introduced that the results in the mouse colitis model and gastritis model showed that TBY-robot can increase the drug enrichment of the inflammatory site by about 1000 times, greatly reducing the inflammatory response and alleviating the symptoms of the disease. This means that TBY-robot is able to actively target more drugs to inflammatory lesions through EMS strategies. ,

At present, micro-nano robots still have problems such as complex preparation methods and limited power systems, and they can only be innovated and developed by integrating with synthetic biology. Cai Lintao, the corresponding author of the paper, said that the research results provide new technical means for the treatment of gastrointestinal inflammation, and also provide new ideas for the treatment of other inflammatory diseases.

“Yeast micro-nano biorobots have excellent biocompatibility and can be used as natural nanomedicine warehouses to accurately deliver different forms of drugs to inflammatory lesions.” Cai Lintao introduced that inflammation is closely related to many diseases, including cancer, obesity, diabetes and brain degenerative diseases, and the team has applied for 5 related invention patents, which will further expand the application scope of dual-engine yeast robots. (Source: China Science News, Diao Wenhui)

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