Common conditional pathogenic bacteria Pseudomonas aeruginosa (Pseudomonas aeruginosa 5) is one of the main pathogens infected in hospitals. Patients with metabolic diseases, hematologic diseases and malignant tumors, as well as patients after surgery or after certain treatments are susceptible to this bacteria. In intensive care unit , P..aeruginosa is also prone to acute pneumonia, causing severe patients to prolong the intubation time and significantly increase the risk of death. Therefore, antibacterial treatment is the key to determining the prognosis of in bacterial pneumonia.
Recently, in a new proof of concept study published on "Nature Materials" , a research team from HD University of California, San Diego has developed an algae -nanoparticle hybrid microrobot for in vivo treatment of lung infection in . In a mouse model of pneumonia with acute P. aeruginosa infection, the microrobot significantly reduced bacterial load and greatly reduced animal mortality. More importantly, this new method uses only a very small amount of antibiotics. The research paves the way for the development of in vivo micro-robots to treat human bacterial pneumonia.
In the past decade, the potential of micro nanorobots in biomedical applications has been widely explored. Early micro-robots were mainly composed of rigid metal or polymer structures for in vitro applications. In recent years, a variety of new robotic platforms have provided more unique advantages for in vivo surgery, including improved drug delivery, deep tissue imaging and precision microsurgery. However, the use of micro-robots in vivo is limited due to the availability of natural materials, the accessibility and potential toxicity of certain organs, tissues, and the active mobility in biological fluids.
In this new study, the team created a biomixing microrobot, which consists of microalgae Chlamydomonas reinhardtii, modified by polymer nanoparticles wrapped in neutrophil membranes and loaded with drug. This algae- nanorobot can be used to treat lung infections or other diseases in the body.
In order to convert microalgae into algae-nanoparticle robots, the researchers first modified the algae surface with azide N-hydroxysuccinimide (NHS) ester, and then coupled with dibenzocyclooctyne (DBCO)-modified neutrophil membrane-coated polymer nanoparticles through click chemical (technology that won the 2022 Nobel Prize in Chemistry ). This type of reaction has been used for cell modification in a variety of applications.
Unmodified microalgae (left) and algae-nanobot (right)
researchers observed that algae-nanobot showed motility and drug-carrying capabilities in simulated lung fluid (SLF). It is worth noting that 95% of algae survived after 1 hour of exercise in SLF, reflecting the good adaptability of algae under these conditions. In addition, due to the uniform distribution of algae, macrophage phagocytosis can be effectively inhibited.
Next, the researchers examined the ability of algae-nanobots to treat acute lung infections in a mouse model inoculated with P.aeruginosa. The experimental results showed that during the 14-day experiment of , the bacterial load of mice treated with algae-nanobots was reduced by 3 orders of magnitude than that of the control group, and all mice survived. In stark contrast, all untreated mice died within three days.
Then, they compared the effects of algae-nanobots with conventional treatments in venously. The therapeutic effect of algae-nanobots is significantly better than intravenous injection at the same drug dose. In fact, the intravenous dose must be 3000 times higher than the dose loaded on algae cells to achieve the same effect in mice.
researchers believe that this micro-robot has the potential to increase the permeability of antibiotics, killing Pseudomonas aeruginosa and ultimately saving more lives.
In addition, nanoparticles and algae will naturally degrade in the body, and their toxicity can be ignored.
In summary, these results demonstrate the combination of targeted drug delivery with active microalgae movement to improve the efficacy of treating bacterial pneumonia.The team's next step will further study how algae-nanomicrobots interact with the immune system, and then scale up the research in preparation for trials in larger animals and ultimately in humans.
paper link:
https://www.nature.com/articles/s41563-022-01360-9
