Macrophages that guard tissue could usher in targeted treatments
Macrophages that guard tissue could usher in targeted treatments lead image
Macrophages are the first line of defense in the immune system, identifying threats and determining the appropriate response. If harnessed, this ability could be used to develop targeted therapies.
Aiassa et al. reviewed macrophage biology and engineering considerations for taking advantage of such biology using tuberculosis treatment as a case study.
“If I have to define macrophages in one word, I would opt for sentinels,” said author Loris Rizzello. “They efficiently spot a plethora of internal (like cancer cells) and external (invading bacteria and viruses) threats. They can remove these threats immediately or recruit other immune cells for a more effective response. They are also super resilient – they can engulf and degrade an enormous amount of external material without undergoing cell suicide.”
Though macrophages occur in all tissues, they evolved to accommodate the distinct needs of each. For instance, alveolar macrophages, found in the lungs, can replicate and efficiently repair damage by remodulating the extracellular matrix without harming neighboring tissue.
By identifying the unique cell profiles involved in the immune response, nanoparticles can be designed to specifically target multiple cells and deliver drugs or act as therapeutic agents.
“We can target a specific phenotypic class by exploiting the concept of avidity to create a multiplexed nanoparticle with ligands with low affinity towards the target receptors,” Rizzello said. “For tuberculosis, the main targets are the alveolar macrophages, but we must keep all other macrophages and cells completely untouched. We envision a loaded drug directed towards infected macrophages in the lung and avoiding any undesired off-targets.”
The authors encourage other scientists to explore the potential for nanoparticles to combat disease in this way.
Source: “The multivalency game ruling the biology of immunity,” by Lara Victoria Aiassa, Giuseppe Battaglia, and Loris Rizzello, Biophysics Reviews (2023). The article can be accessed at https://doi.org/10.1063/5.0166165 .
