Key points from article :
Japanese researchers have developed a new “stealth” coating for nanoparticles that allows drug carriers to evade the body’s immune system for over 100 hours, without relying on the standard polyethylene glycol (PEG) layer. The study, led by scientists at Japan’s Innovation Center of NanoMedicine, describes how tightly linking positive and negative charges into an ion-pair network creates a smooth, non-sticky surface that prevents proteins from attaching and immune cells from recognizing the particles.
In lab and animal experiments, the team engineered polyion complex micelles (30 nm) and vesicles (100 nm) by mixing oppositely charged polymers and stabilizing them with light chemical crosslinks. Once the degree of crosslinking passed a certain threshold—around 40% for micelles and 30% for vesicles—the particles became effectively “invisible” to immune macrophages and resisted protein buildup. These shielded nanoparticles stayed in the bloodstream for up to 121 hours, compared to minutes for unmodified ones.
When filled with the enzyme asparaginase, the nanoparticles acted as tiny bioreactors that broke down asparagine, an amino acid some aggressive cancers depend on to survive. In mouse models of breast and pancreatic cancer, this “starvation therapy” shrank tumours, reduced metastases, and made anti–PD-1 immunotherapy drugs more effective by loosening dense tumour tissue.
The findings suggest a promising new strategy for long-circulating, enzyme-based nanomedicines that can work without PEG, overcoming stability and immune reaction challenges. Beyond cancer treatment, the ion-pair stealth coating could help create next-generation drug delivery systems that stay active in the body far longer while minimizing immune side effects.
