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

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.