nn0c02821_si_003.avi (10.43 MB)
Download fileInterrogation of Folic Acid-Functionalized Nanomedicines: The Regulatory Roles of Plasma Proteins Reexamined
media
posted on 2020-10-21, 12:14 authored by Huan Wang, Tianhao Ding, Juan Guan, Xia Liu, Jing Wang, Pengpeng Jin, Shuangxing Hou, Weiyue Lu, Jun Qian, Weiping Wang, Changyou ZhanFolic acid (FA) has been extensively
exploited to facilitate targeted
delivery of nanomedicines by recognizing the folate receptor-α
(FR-α) overexpressed in many human cancers. Unfortunately, none
have been approved for clinical use yet. Here we reveal that FA functionalization
induces heavy natural IgM absorption on the liposomal surface, depriving
FA of receptor recognition and accelerating complement activation in vivo. FA functionalization does not enhance distribution
of liposomes in FR-α-overexpressed tumors in comparison to plain
liposomes (without FA), but leads to aggravated capture of liposomes
by macrophages in the tumor, liver, and spleen. In addition, FA-functionalized
polymeric nanoparticles are also vulnerable to natural IgM absorption.
This work highlights the pivotal roles of natural IgM in regulating in vivo delivery of FA-functionalized nanomedicines. Due
to the prevalent association of immune disorders and varying levels
of immunoglobulins with cancer patients, extraordinary cautiousness
is urged for clinical translation of FA-enabled targeted delivery
systems.