Brachytherapy is considered to be an unparalleled form of conformal
radiation therapy, which involves the delivery of radiation directly to
tumor lesions or the postoperative cavity. With the development of specific applicators, the exploitation of in situ drug-delivery platform introduces opportunities for the synchronous administration of radiosensitizers. In this study, an
iodine-131 (I131)-labeled
injectable thermosensitive methoxy poly(
ethylene glycol)-b-poly(
tyrosine)
hydrogel (denoted as PETyr-I131) was developed via a facile method. The radioactive source of I131 was immobilized at the
subcutaneous injection site and monitored via single-photon emission computed tomography in real time, and hematological and histopathological analyses revealed no obvious side effects. Additionally, the
SmacN7 peptide conjugated with cell membrane-permeable oligosarginine (denoted as SmacN7-R9) was used to enhance the radiosensitivity of
cancer cells, as confirmed by the results of
reactive oxygen species detection, DNA damage assay, cell apoptosis assay, and clonogenic evaluation. Importantly, a synergistic
brachytherapy treatment effect on
tumor-bearing nude mice was achieved. The proposed thermosensitive supramolecular
hydrogel platform, which conformally immobilizes
radionuclides and delivers radiosensitizers by virtue of its proximity to the site of the primary
tumor or the postoperative cavity, has great potential for achieving synergistic treatment outcomes with reduced radiation-related side effects. STATEMENT OF SIGNIFICANCE: In this work, a kind of radioiodinated thermosensitive supramolecular
hydrogel was developed, which was facilely used as the radioactive source for
brachytherapy. Meanwhile, SmacN7-R9
peptide was combined as a model radiosensitizer to facilitate the activation of
tumor cell apoptosis pathways and promotion of radiation-induced cytotoxicity. Synergistic
brachytherapy outcomes were achieved from the in vitro and in vivo evaluations. Therefore, from the practical standpoint, this thermosensitive supramolecular
hydrogel platform holds great potential for the 3D-conformally immobilizing
radionuclide and delivering radiosensitizer by virtue of its proximity to the site of primary
tumor lesions or postoperative cavity, resulting in synergetic treatment outcomes with reduced radiation associated side effects.