EGFR-targeted antisense oligonucleotides modified with boron clusters offer an innovative approach to cancer chemo-radiotherapy

Suppression of cancer-associated EGFR expression by antisense oligonucleotides is an attractive strategy to augment the efficacy of radiotherapy in cancer treatment. Boron clusters act as selective ligands for the epidermal growth factor receptor (EGFR) and provide an innovative platform for the delivery of naked boron cluster-conjugated therapeutic nucleic acids to cancer cells. Here, we demonstrate that the novel inhibitor B-ASOLNA-CHOL can also enhance efficient and cancer cell-selective uptake via the low-density lipoprotein receptor (LDLR). This conjugate exhibit strong cytotoxic effects on skin and liver cancer cells in combination with BNCT or XRT. We confirmed that intratumoral injections of B-ASOLNA-CHOL combined with local XRT significantly reduced tumor size and EGFR expression in human A431 xenografts implanted in immunodeficient mice. Our findings suggest that B-ASO-CHOL containing a CpG ODN motif exhibits immune adjuvant properties. The results underscore the potential of B-ASOLNA-CHOL technology for therapeutic applications in radiation immuno-oncology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/668562v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@a275edorg.highwire.dtl.DTLVardef@1ec2c5eorg.highwire.dtl.DTLVardef@54fc6aorg.highwire.dtl.DTLVardef@187bd60_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG