Folic Acid Enables Targeting Delivery of Lipodiscs by Circumventing IgM-Mediated Opsonization

Folic acid (FA) is one of the most widely utilized small-molecule ligands for cancer targeted drug delivery. Natural IgM was recently found to avidly absorb on the surface of FAfunctionalized liposomes (FA-sLip), negatively regulating the in vivo performance by efficiently activating complement. Herein, FAfunctionalized lipodiscs (FA-Disc) were constructed to successfully circumvent IgM-mediated opsonization and retained binding activity with folate receptors in vivo. The FA moiety along with the bound IgM was restricted to the highly curved rim of lipodiscs, leading to IgM incapability of presenting the membrane-bound conformation to trigger complement activation. The C1q docking, C3 binding, and C5a release were blocked and accelerated blood clearance phenomenon was mitigated of FA-Disc. FA-Disc retained folate binding activity and could effectively target folate receptor positive tumors in vivo. The present study provides a useful solution to avoid the negative regulation by IgM and achieve FA-enabled targeting by exploring disc-shaped nanocarriers.

Automated summary

In this study, folic acid-functionalized lipodiscs (FA-Disc) were successfully constructed to avoid opsonization by IgM and achieve folate targeting. FA-Disc retained folate binding activity and could effectively target folate receptor positive tumors in vivo. This study provides a solution to avoid negative regulation by IgM and achieve folate-enabled targeting by exploring disc-shaped nanocarriers.