TY - JOUR
T1 - Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window
AU - Wang, Xu
AU - Wilhelm, Jonathan
AU - Li, Wei
AU - Li, Suxin
AU - Wang, Zhaohui
AU - Huang, Gang
AU - Wang, Jian
AU - Tang, Houliang
AU - Khorsandi, Sina
AU - Sun, Zhichen
AU - Evers, Bret
AU - Gao, Jinming
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Stimuli-sensitive nanomaterials with cooperative response are capable of converting subtle and gradual biological variations into robust outputs to improve the precision of diagnostic or therapeutic outcomes. In this study, we report the design, synthesis and characterization of a series of degradable ultra-pH sensitive (dUPS) polymers that amplify small acidic pH changes to efficacious therapeutic outputs. A hydrolytically active polycarbonate backbone is used to construct the polymer with pH-dependent degradation kinetics. One dUPS polymer, PSC7A, can achieve activation of the stimulator of interferon genes and antigen delivery upon endosomal pH activation, leading to T cell-mediated antitumor immunity. While a non-degradable UPS polymer induces granulomatous inflammation that persists over months at the injection site, degradable PSC7A primes a transient acute inflammatory response followed by polymer degradation and complete tissue healing. The improved therapeutic window of the dUPS polymers opens up opportunities in pH-targeted drug and protein therapy.
AB - Stimuli-sensitive nanomaterials with cooperative response are capable of converting subtle and gradual biological variations into robust outputs to improve the precision of diagnostic or therapeutic outcomes. In this study, we report the design, synthesis and characterization of a series of degradable ultra-pH sensitive (dUPS) polymers that amplify small acidic pH changes to efficacious therapeutic outputs. A hydrolytically active polycarbonate backbone is used to construct the polymer with pH-dependent degradation kinetics. One dUPS polymer, PSC7A, can achieve activation of the stimulator of interferon genes and antigen delivery upon endosomal pH activation, leading to T cell-mediated antitumor immunity. While a non-degradable UPS polymer induces granulomatous inflammation that persists over months at the injection site, degradable PSC7A primes a transient acute inflammatory response followed by polymer degradation and complete tissue healing. The improved therapeutic window of the dUPS polymers opens up opportunities in pH-targeted drug and protein therapy.
UR - http://www.scopus.com/inward/record.url?scp=85096099772&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096099772&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-19651-7
DO - 10.1038/s41467-020-19651-7
M3 - Article
C2 - 33203928
AN - SCOPUS:85096099772
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5828
ER -