Exploring the crucial role of biomolecular coronas for nanoparticle-cell interactions
(Nanowerk Spotlight) When nanoparticles enter a biological environment – e.g. human blood – they come into immediate contact with various biomolecules, such as proteins. These biomolecules form a coating layer on the nanoparticle surface – the so-called biomolecular corona – thereby imparting a unique biological identity to the nanoparticle, which could be very different from the pristine nanoparticle surface.
They found that the biomolecular corona could act as a personalized 'endogenous trigger' affecting off-target interactions and controlling the indication for disease of clinically approved formulations.
"Therapeutic failure of targeted liposomes renewed questions about understanding limitations in liposome-based drug development," Morteza Mahmoudi, Director of and Principal Investigator at the NanoBio Interactions Laboratory at Tehran University of Medical Sciences, tells Nanowerk. "In our work we have, for the first time, quantitatively demonstrated the ability of the biomolecular corona to switch the mechanism of cellular uptake of liposomes."
Mahmoudi and his co-authors believe that mechanistic investigation of the biomolecular corona could contribute to a better understanding of the poor success of targeted liposomal technology.
They hope that their results will contribute to the design of specific targeted nanoformulations to exploit specific cellular pathways of interest. In this way, physiological response of liposomes – bio-distribution, targeting ability etc. – could be finely tuned. This aspect may have a dramatic application in the emerging field of personalized nanomedicine.
"Some of us have shown that alterations in concentration and structure of plasma proteins as those produced by clinical manifestations of disease lead to formation of 'personalized biomolecular corona'," notes Giulio Caracciolo, an Associate Professor and Principal Investigator of the Nanodelivery Lab, Department of Molecular Medicine ate Sapienza University of Rome, and senior author of the paper. "The personalized biomolecular corona may contribute to better explain why patients display different susceptibility and therapeutic responses to the same drug. This aspect deserves further investigation."
Among other implications, this means that various cell types may employ different pathways to internalize nanoparticles with their own personalized biomolecular corona.
"Clearly, results of our present investigation cannot fully account for the complexity of the in vivo interactions between liposomes and cells," the researchers caution. "To achieve this, will require comprehensive studies entailing libraries of liposomes, biomolecular coronas, and cells."
"Results of our study open the fascinating possibility to manipulate the biomolecular corona by liposome design," they conclude. "This is not an easy task, but it could represent a turning point in the development of novel liposome-based targeting strategies for personalized nanomedicine."