Nanoparticle delivery of a prodrug-activating bacterial enzyme leads to anti-tumor responses.

ABSTRACT: Most cancer patients diagnosed with late-stage head and neck squamous cell carcinoma are treated with chemoradiotherapy, which can lead to toxicity. One potential alternative is tumor-limited conversion of a prodrug into its cytotoxic form. We reason this could be achieved by transient and tumor-specific expression of purine nucleoside phosphorylase (PNP), an Escherichia coli enzyme that converts fludarabine into 2-fluoroadenine, a potent cytotoxic drug. To efficiently express bacterial PNP in tumors, we evaluate 44 chemically distinct lipid nanoparticles (LNPs) using species-agnostic DNA barcoding in tumor-bearing mice. Our lead LNP, designated LNP intratumoral (LNP^IT), delivers mRNA that leads to PNP expression in vivo. Additionally, in tumor cells transfected with LNP^IT<

SUBMITTER: Huayamares SG 

PROVIDER: S-EPMC11993580 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature