(A) Chemical structures and schematic representation of the radiation triggered release of drug and small AuNP payloads from Se-PCPP hydrogel. (B) Photograph of the Se-PCPP hydrogel loaded with 405 μg quisinostat and 10 mg of AuNP per 1 mg of PCPP, before and after the vial inversion test. (C) Photograph of the Se-PCPP hydrogel nonloaded, or loaded with 10 mg of AuNP, 370 μg of doxorubicin, or 46 μg of FITC-BSA per 1 mg of PCPP (left to right) with some excess water on top of the hydrogel for storage purposes. (D) UV–vis spectra of Se-PCPP hydrogel loaded with increasing amounts of AuNP (from 1 to 10 mg AuNP per 1 mg PCPP) compared to free AuNP and acquired at constant gold concentration. (E) Representative TEM of the Se-PCPP hydrogel in dry state loaded with 5 mg AuNP per 1 mg PCPP. Scale bar = 50 nm. (F) FT-IR spectra of the nonloaded (orange) and AuNP loaded (blue) Se-PCPP hydrogel and comparison to free selenocystamine (red) and free PCPP (gray). Comparison of the release (after 7 days incubation) of (G) AuNP and (H) drug between mock irradiation (left) and 60 Gy radiation triggered degradation (right) from the Se-PCPP hydrogel containing quisinostat (orange), doxorubicin (red), or FITC-BSA (green). (I) Viability of U251 (blue) and NS039 (red) cells after incubation with cell medium treated with either the eluted drug from the non-irradiated Se-PCPP loaded with quisinostat, or the radiation released drug from the Se-PCPP loaded with quisinostat and irradiated with 60 Gy. (J) Viability of NS039 cells without (black) or with 8 Gy irradiation, (gray) and treated with either vehicle, the nondegradable hydrogel loaded with quisinostat and our X-ray degradable hydrogel loaded with quisinostat. ** and *** indicate a difference at p < 0.01 or 0.001, respectively.