Selenium Nanoparticles Synergize with a KRAS Nanovaccine against Breast Cancer

硒纳米颗粒与KRAS纳米疫苗协同作用对抗乳腺癌

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作者:Cláudio Ferro ,Ana I Matos ,Luigia Serpico ,Flavia Fontana ,Jacopo Chiaro ,Carmine D'Amico ,Alexandra Correia ,Risto Koivula ,Marianna Kemell ,Maria Manuela Gaspar ,Rita C Acúrcio ,Vincenzo Cerullo ,Hélder A Santos ,Helena F Florindo

Abstract

Selenium (Se) is an element crucial for human health, known for its anticancer properties. Although selenium nanoparticles (SeNPs) have shown lower toxicity and higher biocompatibility than other Se compounds, bare SeNPs are unstable in aqueous solutions. In this study, several materials, including bovine serum albumin (BSA), chitosan, polymethyl vinyl ether-alt-maleic anhydride, and tocopherol polyethylene glycol succinate, are explored to develop stable SeNPs and further evaluate their potential as candidates for cancer treatment. All optimized SeNP are spherical, <100 nm, and with a narrow size distribution. BSA-stabilized SeNPs produced under acidic conditions present the highest stability in medium, plasma, and at physiological pH, maintaining their size ≈50-60 nm for an extended period. SeNPs demonstrate enhanced toxicity in cancer cell lines while sparing primary human dermal fibroblasts, underscoring their potential as effective anticancer agents. Moreover, the combination of BSA-SeNPs with a nanovaccine results in a strong tumor growth reduction in an EO771 breast cancer mouse model, demonstrating a three-fold decrease in tumor size. This synergistic anticancer effect not only highlights the role of SeNPs as effective anticancer agents but also offers valuable insights for developing innovative combinatorial approaches using SeNPs to improve the outcomes of cancer immunotherapy.

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