| Sumario: | Purpose: Enhancing therapeutic effectiveness is crucial for translating anticancer nanomedicines from laboratory to clinical settings. In this study, we have developed radioactive rhenium oxide nanoparticles encapsulated in human serum albumin ([188Re]ReOx-HSA NPs) for concurrent radiotherapy (RT) and photothermal therapy (PTT), aiming to optimize treatment outcomes. Methods: [188Re]ReOx-HSA NPs were synthesized by a controlled reduction of 188ReO4− in HSA medium and extensively characterized. The anticancer effect of [188Re]ReOx-HSA NPs was demonstrated in vitro in murine melanoma (B16F10) cell line. In vivo SPECT/CT imaging, autoradiography and biodistribution studies were performed after intratumoral injection of [188Re]ReOx-HSA NPs in melanoma tumor-bearing C57BL/6 mice. The potential of [188Re]ReOx-HSA NPs for combined RT and PTT treatment was also demonstrated in the aforesaid mice model. Results: [188Re]ReOx-HSA NPs (size 4–6 nm) were synthesized with high colloidal and radiochemical stability. Upon laser (808 nm) exposure on B16F10 cells incubated with [188Re]ReOx-HSA NPs, only < 20% of cells were alive demonstrating high therapeutic efficacy under in vitro settings. Uniform dose distribution and retention of the radiolabeled NPs in the tumor volume were observed via SPECT/CT imaging and autoradiography studies. Tumor growth in mice model was significantly arrested with ~ 1.85 MBq dose of [188Re]ReOx-HSA NPs and simultaneous laser irradiation, demonstrating synergistic benefit of RT and PTT. Conclusions: These results demonstrate that intrinsically radiolabeled [188Re]ReOx-HSA NPs having unique features such as high photothermal effects and favorable nuclear decay characteristics for combined RT/PTT, hold great promise for clinical translation.
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