Protein-functionalized and intrinsically radiolabeled [188Re]ReOx nanoparticles: advancing cancer therapy through concurrent radio-photothermal effects

Abstract

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]ReO_x-HSA NPs) for concurrent radiotherapy (RT) and photothermal therapy (PTT), aiming to optimize treatment outcomes.

Methods

[¹⁸⁸Re]ReO_x-HSA NPs were synthesized by a controlled reduction of ¹⁸⁸ReO₄⁻ in HSA medium and extensively characterized. The anticancer effect of [¹⁸⁸Re]ReO_x-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]ReO_x-HSA NPs in melanoma tumor-bearing C57BL/6 mice. The potential of [¹⁸⁸Re]ReO_x-HSA NPs for combined RT and PTT treatment was also demonstrated in the aforesaid mice model.

Results

[¹⁸⁸Re]ReO_x-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]ReO_x-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]ReO_x-HSA NPs and simultaneous laser irradiation, demonstrating synergistic benefit of RT and PTT.

Conclusions

These results demonstrate that intrinsically radiolabeled [¹⁸⁸Re]ReO_x-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.

Graphical Abstract