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Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window

Author

Listed:
  • Xu Wang

    (University of Texas Southwestern Medical Center)

  • Jonathan Wilhelm

    (University of Texas Southwestern Medical Center)

  • Wei Li

    (University of Texas Southwestern Medical Center)

  • Suxin Li

    (University of Texas Southwestern Medical Center)

  • Zhaohui Wang

    (University of Texas Southwestern Medical Center)

  • Gang Huang

    (University of Texas Southwestern Medical Center)

  • Jian Wang

    (University of Texas Southwestern Medical Center)

  • Houliang Tang

    (University of Texas Southwestern Medical Center)

  • Sina Khorsandi

    (University of Texas Southwestern Medical Center)

  • Zhichen Sun

    (University of Texas Southwestern Medical Center)

  • Bret Evers

    (University of Texas Southwestern Medical Center)

  • Jinming Gao

    (University of Texas Southwestern Medical Center)

Abstract

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.

Suggested Citation

  • Xu Wang & Jonathan Wilhelm & Wei Li & Suxin Li & Zhaohui Wang & Gang Huang & Jian Wang & Houliang Tang & Sina Khorsandi & Zhichen Sun & Bret Evers & Jinming Gao, 2020. "Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19651-7
    DOI: 10.1038/s41467-020-19651-7
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    Cited by:

    1. Lilong Liu & Yaxin Hou & Changqi Deng & Zhen Tao & Zhaohui Chen & Junyi Hu & Ke Chen, 2022. "Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Jian Cheng & Guihai Gan & Shaoqiu Zheng & Guoying Zhang & Chen Zhu & Shiyong Liu & Jinming Hu, 2023. "Biofilm heterogeneity-adaptive photoredox catalysis enables red light-triggered nitric oxide release for combating drug-resistant infections," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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