Electrostatically motivated design of biomimetic nanoparticles: Promoting specific adhesion and preventing nonspecific adhesion simultaneously

Receptor-ligand (RL) interaction mediated specific adhesion of nanoparticles (NPs) to plasma membranes (PMs) is significant for targeted drug delivery, imaging of cellular processes, etc. A major challenge associated with any specific adhesion process is the possible nonspecific adhesion (NSA) of the introduced NPs to healthy, non-targeted cells leading to cytotoxicity and other problems. In this letter, we propose an electrostatically motivated design of biomimetic NPs where the promotion of specific adhesion and the prevention of NSA may be simultaneously ensured. We consider a lipid bilayer (LBL) encapsulated NP (LBLENP) that interacts with the plasma membrane (PM) of any cell in a manner such that at physiological conditions, the LBLENP-PM electrostatic repulsion outweighs attractive influences (e.g., thermal fluctuations and van der Waals effect) at a critical separation distance d_g,c,1. We argue that the very presence of a finite d_g,c,1 will suffice to prevent the NSA, while designing ligands on the LBLENP in a manner such that d_RL > d_g,c,1 (d_RL being the length of the R-L complex formed by the interaction of the ligands with the membrane receptors) will ensure a R-L mediated specific adhesion.