Fig. 9.

(A) Addition of a supplemental component (termed a SORT molecule) to traditional LNPs systematically alters the in vivo delivery profile and mediates tissue-specific delivery as a function of the percentage and biophysical property of the SORT molecule [150]. Reproduced with the permission from Ref 151. Copyright © 2021 Springer Nature. (B) iPhos lipid design directs LNP tissue targeting. Zwitterion iPhos lipids contain two lipid tails on the positively charged tertiary amine and one lipid tail on the negatively charged phosphate group. Varying the alkyl lipid chain length impacts tissue targeting to liver, lung and spleen, which has been coined selective organ targeting (SORT) [151]. Reproduced with the permission from Ref 151. Copyright © 2021 Springer Nature. (C) Schematic representation of the formation of a disulfide bond between PDP-functionalized lipids that are incorporated into the liposome bilayer and reduced exofacial thiol groups, present at the cell surface [152]. Reproduced with the permission from Ref 152. Copyright © 2016 Elsevier.