Brachytherapy, as an effective setting for precise
cancer therapy in clinic, can lead to serious DNA damage. However, its therapeutic efficacy is always limited by the
DNA self-repair property, tumor hypoxia-associated radiation resistance as well as inhomogeneous distribution of the radioactive material. Herein, a multifunctional hybrid
hydrogel (131 I-
hydrogel/DOX/GNPs aggregates) is developed by loading
gold nanoparticle aggregates (GNPs aggregates) and DOX into a
radionuclide iodine-131 (131 I) labelled polymeric
hydrogels (131 I-PEG-P(Tyr)8 ) for
tumor destruction by completely damaging
DNA self-repair functions. This hybrid
hydrogel exhibits excellent photothermal/radiolabel stability, biocompatibility, and fluorescence/photothermal /SPECT imaging properties. After local injection, the sustained releasing DOX within
tumor greatly inhibits the DNA replication. Meanwhile, GNPs aggregates as a radiosensitizer and
photosensitizer show a significant improvement of brachytherapeutic efficacy and cause serious DNA damage. Simultaneously, GNPs aggregates induce mild
photothermal therapy under 808 nm
laser irradiation, which not only inhibits self-repair of the damaged
DNA but also effectively relieves
tumor hypoxic condition to enhance the
therapeutic effects of
brachytherapy, leading to a triple-synergistic destruction of
DNA functions. Therefore, this study provides a highly efficient
tumor synergistic
therapy platform and insight into the synergistic antitumor mechanism in
DNA level.