Evaluating metal nanoparticle radiosensitisers with DNA repair inhibitors: a novel theranostic approach in primary glioblastoma

Finally, the novel impact of differentially PEGylated gold NPs and radiation on GBM cell immune modulation was determined by cytokine arrays.<br><br>We found that AGuIX and ID11 in U-87 MG cells, and AGuIX, ID11, and ID12 in U-251 MG cells, potentiated the radiation response by enhancing DNA double-strand break (DSB) induction. Combination studies with these NPs and DDRIs (Olaparib, AZD0156, and AZD6738) identified four optimised NP-DDRI combinations with synergistic effects on GBM cell survival.

The combinations include AGuIX and AZD6738 in U-87 MG cells, and ID11 and AZD0156, AGuIX and Olaparib, and ID12 and Olaparib in U-251 MG cells. Persistent DSBs were elucidated as an underlying mechanism of enhanced radiosensitization. The observed synergy provides valuable insight into the types of DNA lesions generated by each NP and the preferential mechanisms of repair.

Our data demonstrate the synergistic potential of metal NPs and DDRIs that could improve the efficacy of RT in preclinical GBM models.<br><br>Cytokine expression changes in response to the differentially PEGylated GNPs and RT showed ID11 (PEG = 4) caused the greatest boost in RT immunogenicity. This desirable immune modulation highlights the therapeutic potential of GNP-RT combinations for greater tumour control in GBM patients in the future.<br><br>