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

Xu Wang¹, Jonathan Wilhelm¹, Wei Li¹

¹Department of Pharmacology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Nature Communications

|November 18, 2020

Summary

Researchers developed degradable ultra-pH sensitive (dUPS) polymers that amplify small pH changes for precise therapeutic outcomes. These novel polymers activate immune responses and degrade, avoiding persistent inflammation for improved drug and protein delivery.

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Area of Science:

Biomaterials Science
Nanotechnology
Immunology

Background:

Stimuli-sensitive nanomaterials offer precise diagnostic and therapeutic potential by amplifying biological variations.
Developing materials that respond to subtle pH changes is crucial for targeted therapies.

Purpose of the Study:

To design, synthesize, and characterize degradable ultra-pH sensitive (dUPS) polymers.
To investigate the amplification of small acidic pH changes into therapeutic outputs.
To evaluate the in vivo performance and safety of dUPS polymers compared to non-degradable counterparts.

Main Methods:

Synthesis of a series of degradable polymers utilizing a hydrolytically active polycarbonate backbone.
Characterization of pH-dependent degradation kinetics.
In vivo assessment of polymer-induced immune response, therapeutic efficacy, and tissue healing.

Main Results:

The dUPS polymer PSC7A demonstrated activation of interferon genes and antigen delivery upon endosomal pH changes.
PSC7A induced T cell-mediated antitumor immunity.
Unlike persistent inflammation from non-degradable polymers, PSC7A elicited a transient inflammatory response followed by complete tissue healing.

Conclusions:

Degradable ultra-pH sensitive polymers effectively amplify subtle pH variations for enhanced therapeutic outcomes.
The dUPS polymers exhibit a favorable safety profile with complete tissue regeneration.
These findings present new opportunities for pH-targeted drug and protein delivery systems.