A Biodegradable Nucleotide Coordination Polymer for Enhanced NSCLC Therapy in Combination with Metabolic Modulation

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in the treatment of non‐small cell lung cancer (NSCLC) still face challenges of acquired resistance and non‐negligible side effects. To overcome these limitations, a biodegradable coordination polymer using guanine deoxynucleotide and ferrous iron (dGNP) is developed for targeted delivery of EGFR‐TKIs. dGNPs can efficiently target nucleoside transporters in tumor cells that are regulated by fasting‐mimicking diet (FMD). Meanwhile, FMD can augment the therapeutic efficacy of EGFR‐TKIs by suppressing EGFR tyrosine kinase phosphorylation and related downstream pathways. In vivo results demonstrate that EGFR‐TKIs‐laden dGNPs combined with FMD treatment exhibit superior antitumor efficacy and reduced side effect. This study provides an innovative approach to enhance the therapeutic efficacy of EGFR‐TKIs through nucleotide nanocarrier and metabolic modulation.