Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility

Abstract

Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics.

Keywords:

• Curdlan
• PEGylation
• cytotoxicity
• LD50
• siRNA delivery

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was kindly supported by the National Natural Science Foundation of China (Grant number: 21875124) and Natural Science Foundation of Inner Mongolia Autonomous Region (Grant numbers: 2019MS02009, 2021MS02009).