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Neurotoxicity Profiling of Aluminum Salt-Based Nanoparticles as Adjuvants for Therapeutic Cancer Vaccine.
Chen, Chen; Xue, Changying; Jiang, Jiaxuan; Bi, Shisheng; Hu, Zurui; Yu, Ge; Sun, Bingbing; Mao, Chuanbin.
Affiliation
  • Chen C; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Xue C; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Jiang J; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Bi S; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Hu Z; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Yu G; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Sun B; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
  • Mao C; State Key Laboratory of Fine Chemicals (C.C., J.J., S.B., Z.H., G.Y., B.S.), School of Bioengineering (C.C., C.X.), School of Chemical Engineering (J.J., S.B., Z.H., G.Y., B.S.), and Frontiers Science Center for Smart Materials Oriented Chemical Engineering (C.C., J.J., S.B., Z.H., G.Y., B.S.), Dali
J Pharmacol Exp Ther ; 390(1): 45-52, 2024 Jun 21.
Article in En | MEDLINE | ID: mdl-38272670
ABSTRACT
Therapeutic vaccines containing aluminum adjuvants have been widely used in the treatment of tumors due to their powerful immune-enhancing effects. However, the neurotoxicity of aluminum adjuvants with different physicochemical properties has not been completely elucidated. In this study, a library of engineered aluminum oxyhydroxide (EAO) and aluminum hydroxyphosphate (EAHP) nanoparticles was synthesized to determine their neurotoxicity in vitro. It was demonstrated that the surface charge of EAHPs and size of EAOs did not affect the cytotoxicity in N9, bEnd.3, and HT22 cells; however, soluble aluminum ions trigger the cytotoxicity in three different cell lines. Moreover, soluble aluminum ions induce apoptosis in N9 cells, and further mechanistic studies demonstrated that this apoptosis was mediated by mitochondrial reactive oxygen species generation and mitochondrial membrane potential loss. This study identifies the safety profile of aluminum-containing salts adjuvants in the nervous system during therapeutic vaccine use, and provides novel design strategies for their safer applications. SIGNIFICANCE STATEMENT In this study, it was demonstrated that engineered aluminum oxyhydroxide and aluminum hydroxyphosphate nanoparticles did not induce cytotoxicity in N9, bEnd.3, and HT22 cells. In comparation, soluble aluminum ions triggered significant cytotoxicity in three different cell lines, indicating that the form in which aluminum is presenting may play a crucial role in its safety. Moreover, apoptosis induced by soluble aluminum ions was dependent on mitochondrial damage. This study confirms the safety of engineered aluminum adjuvants in vaccine formulations.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adjuvants, Immunologic / Apoptosis / Cancer Vaccines / Nanoparticles Limits: Animals / Humans Language: En Journal: J Pharmacol Exp Ther / J. pharmacol. exp. ther. (Online) / The journal of pharmacology and experimental therapeutics (Online) Year: 2024 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adjuvants, Immunologic / Apoptosis / Cancer Vaccines / Nanoparticles Limits: Animals / Humans Language: En Journal: J Pharmacol Exp Ther / J. pharmacol. exp. ther. (Online) / The journal of pharmacology and experimental therapeutics (Online) Year: 2024 Document type: Article