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 PMID:33203928  

Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window.

Xu Wang | Jonathan Wilhelm | Wei Li | Suxin Li | Zhaohui Wang | Gang Huang | Jian Wang | Houliang Tang | Sina Khorsandi | Zhichen Sun | Bret Evers | Jinming Gao
Nature communications | 2020

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.

Pubmed ID: 33203928

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA216839
  • Agency: NCI NIH HHS, United States
    Id: U01 CA218422
  • Agency: NCI NIH HHS, United States
    Id: U54 CA244719

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