Journal
ACS NANO
Volume 14, Issue 11, Pages 14779-14789Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c02821
Keywords
folic acid; nanomedicine; immunoglobulin; natural IgM; liposome
Categories
Funding
- National Natural Science Foundation of China [81973245, 81673361, 81673370, 81690263]
- China Postdoctoral Science Foundation [2019M651385]
- Shanghai Municipal Commission of Health and Family Planning [2018BR04]
- Shanghai Natural Science Foundation [19431900300, 18ZR1404800]
- Pudong New Area Commission of Science Technology [PKJ2016-Y46]
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Folic acid (FA) has been extensively exploited to facilitate targeted delivery of nanomedicines by recognizing the folate receptor-alpha (FR-alpha) 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-alpha-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.
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