Nanomicelles of Radium Dichloride [223Ra]RaCl2 Co-Loaded with Radioactive Gold [198Au]Au Nanoparticles for Targeted Alpha–Beta Radionuclide Therapy of Osteosarcoma

Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 (223Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold (198Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [223Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([198Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [223Ra]Ra nanomicelles co-loaded with [198Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression

Short-range antiferromagnetic interaction and spin-phonon coupling in La2CoMnO6 double perovskite

arXiv:1802.07326v3Weak antiferromagnetic (AFM) interaction in the ferromagnetic (FM) partially ordered La2CoMnO6 (LCMO) was detected by Raman spectroscopy by monitoring spin-phonon coupling. Because of the sensibility to probe short-range disorder and lattice modifications, the Raman spectroscopy showed to be an useful tool to indicate less remarkable magnetic transitions in LCMO compound. Apart from the expected spin-phonon coupling due to the long-range FM superexchange (Tc ∼230 K), phonons parameters pointed out an additional spin-phonon coupling related to the short-range AFM interaction at Tc ∼135 K, which was not detected from the magnetic bulk response. These results reinforce the Raman spectroscopy as a powerful technique to detect antisite disorder into A2B′B’’O6 magnetic double perovskites, whose magnetic properties are driven by superexchange interactions.The authors thank the Brazilian agencies, Conselho Nacional de Desenvolvimento Científico e Tecnológico- CNPq, Brazil (UNIVERSAL 431943/2016-8, PQ - 305806/2020-3), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES, Brazil, Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG, Brazil, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico - FUNCAP, Brazil, and Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão - FAPEMA, Brazil (UNIVERSAL-01290/2016; INFRA-02050/21; BPD-05073/21) for co-funding this work.Peer reviewe

Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([²²³Ra]RaCl₂): Understanding the Effect on Cell Structure

The use of alpha-particle (α-particle) radionuclides, especially [223Ra]RaCl2 (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [223Ra] RaCl2 on cancer cells. To analyze the effect of [223Ra]RaCl2 on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines

AbstractCancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated (in vitro) in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) (198Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC (198Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC (198Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment