Abstract
Antivirulence therapy has proven to be an attractive method for the treatment of bacterial infections and venomous injuries; however, the approaches for neutralizing multiple types of virulence through one platform are limited. To address this challenge, we have developed a reactive conjugated polymer, PPV–NHS, which functions as a broad-spectrum antidote for directly inactivating basic toxins. The antivirulence is achieved via multivalent electrostatic recognition and subsequent amidation reactions between PPV–NHS and toxins. The resultant bioconjugates significantly reduced neurotoxicity and cytotoxicity. In the mouse model, PPV–NHS effectively inhibited the toxicity of cardiotoxin (CTX) and improved the survival rate of toxin-challenged mice. This work represents the rational design of functionalized conjugated polymers for antivirulence therapy with both high efficiency and broad applicability.
Highlights
Millions of lives are taken away each year due to the pathogenicity caused by biotoxins
The results showed that PPV–NHS selectively binds to basic proteins through electrostatic recognition covalent interactions (Scheme 1a)
horseradish peroxidase (HRP), bilirubin oxidase (BOD), glucose oxidase (GOD), and glucose-6-phosphate dehydrogenase (G6PD) did not react with PPV–NHS even when PPV–NHS was present in excess of 20-fold
Summary
Millions of lives are taken away each year due to the pathogenicity caused by biotoxins. Proteins and peptides from microorganism infections and venomous injuries are the main pathogenic causes[1,2,3]. Antisera[6], antibodies[7], and vaccines[8] are common methods to eliminate toxins. Some small molecules[10], polymers[11,12], and nanomaterials[13,14] have been used for detoxification by binding to specific targets of toxins. The development of materials that recognize and inactive basic protein toxins offers great potential for
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