Synthesis of Poly(acyclic orthoester)s: Acid-Sensitive Biomaterials for Enhancing Immune Responses of Protein Vaccine

Xing, YM (Xing, Yumeng)^{[ 1,2 ]} ; Xu, ZK (Xu, Zunkai)^{[ 1,2 ]} ; Liu, T (Liu, Tao)^{[ 1,2 ]} ; Shi, LQ (Shi, Linqi)^{[ 1,2 ]} ; Kohane, D (Kohane, Daniel)^{[ 3 ]} ; Guo, ST (Guo, Shutao)^{[ 1,2 ]}

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, 59(18): 7235-7239

DOI: 10.1002/anie.202001169

摘要

While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.