Molecular basis for rational construction of RVGP modified liposomal delivery system targeting to brain.

The rational construction of active targeting liposomes will provide an important structural support for its effective brain targeting. However, there is no clear understanding of the structure-activity relationship of active targeting liposomes. Combining multiscale computational simulation and experimental verification, we established a computational model of RVGP modified PEGylated liposomes (RVGP-PEG-L) and investigated the role of PEG and molecular interaction mechanism of carrier-ligand-receptor. The result indicated that the complex network conformation formed by PEG with 42 monomers (42PEG) above the density of 8% was the molecular basis for PEG-L to achieve long-circulation function. The lowest monomer number of PEG linker to ensure the targeting ability of RVGP was 42. However, the pose of RVGP binding to nAChR changed after it was linked with PEG-L due to the restraint of PEG chain, leading to a decrease of binding free energy. Increasing the monomer number of PEG linker or improving the non-polarity of polymers was a potential strategy to enhance the combination of RVGP-PEG-L with nAChR on the targeting cell. [ABSTRACT FROM AUTHOR]