Molecular scale study on the interactions of biocompatible nanoparticles with macrophage membrane and blood proteins

Abstract

Abstract Macrophage targeting and researches centered on immunological responses have received interest thanks to studies unveiling the significant role of macrophages in inflammatory diseases and cancer. In this regard, we have selected four types of nanoparticles (NPs), including acetalated dextran‐based nano‐carrier functionalized with atrial natriuretic peptide and linTT1(AcDEX‐PEG‐TT1‐ANP), PEGylated acetalated dextran (AcDEX‐PEG), acetalated dextran (AcDEX), and hyaluronic acid (HA) to investigate their interactions with macrophage membrane. Using microsecond coarse‐grained molecular dynamics (MD) simulations, we studied the interactions between the NPs and the macrophage membrane and subsequent immunological reactions that occur after the penetration of the NPs within the macrophage cell. Different parameters that determine the strength and amount of macrophage membrane interaction were measured and compared for all four types of NPs. The results showed that AcDEX‐PEG‐TT1‐ANP has the most favorable interaction with the macrophage membrane while HA has the least favorable results by comparison. Moreover, drug encapsulation and release in different pH conditions showed the pH‐responsivity of the considered NPs for drug delivery in acidic environments. On the other hand, evaluations with human serum albumin (HSA), fibrinogen (Fib), and transferrin (Tf) declared that peptide modified AcDEX polymers are the most probable NPs to absorb a layer of the protein corona.

Keywords

• acetalated dextran
• macrophage
• molecular dynamics
• pH‐sensitive release
• protein corona