**4. Conclusions**

In this study, the <sup>225</sup>Ac-rHDL system was prepared and evaluated as a potential targeted radiotherapeutic agent. The results showed adequate physicochemical properties of the rHDL nanocarrier to specifically deposit <sup>225</sup>Ac into the cytoplasm of HEP-G2 and PC-3 cancer cells and produce a significant cell cytotoxic effect. Biodistribution studies of <sup>225</sup>Ac-rHDL in healthy mice showed mainly liver uptake with hepatobiliary and renal excretion without appreciable accumulation in other tissues, while, in tumor-bearing mice, the <sup>225</sup>Ac-rHDL nanosystem remained stable in the tumors and generated ablative radiation doses. The results obtained in this research justify further preclinical studies designed to evaluate the therapeutic efficacy of <sup>225</sup>Ac-rHDL for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor.

**Author Contributions:** Conceptualization, G.F.-F., K.I.-O. and E.M.-Á.; methodology, T.H.-J., B.O.-G., C.S.-C., L.A.-L., M.L.-G. and L.D.N.; formal analysis, E.M.-Á., C.S.-C. and G.F.-F.; writing—original draft preparation, T.H.-J.; writing—review and editing, G.F.-F. and L.M.-A.; funding acquisition, G.F.-F. and K.I.-O.; writing—review, A.R. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Mexican National Council of Science and Technology (CONACyT), grant CB2017-2018-A1-S-36841.

**Institutional Review Board Statement:** This research was approved by the Ethics Internal Committee of Use and Care of Laboratory Animals (CICUAL-ININ) of the National Institute of Nuclear Research, Approval No. 04-2018-2021.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** This study was conducted as a component of the activities of the "Laboratorio Nacional Investigación y Desarrollo de Radiofármacos, CONACyT" (LANIDER).

**Conflicts of Interest:** The authors declare no conflict of interest.

**Sample Availability:** Samples of the compounds not available are available from the authors.
