TY - JOUR
T1 - Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer's Disease Patients
AU - Gagliardi, Stella
AU - Truffi, Marta
AU - Tinelli, Veronica
AU - Garofalo, Maria
AU - Pandini, Cecilia
AU - Cotta Ramusino, Matteo
AU - Perini, Giulia
AU - Costa, Alfredo
AU - Negri, Sara
AU - Mazzucchelli, Serena
AU - Bonizzi, Arianna
AU - Sitia, Leopoldo
AU - Busacca, Maria
AU - Sevieri, Marta
AU - Mocchi, Michela
AU - Ricciardi, Alessandra
AU - Prosperi, Davide
AU - Corsi, Fabio
AU - Cereda, Cristina
AU - Morasso, Carlo
PY - 2022/8/17
Y1 - 2022/8/17
N2 - BACKGROUND: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn).METHODS: We tested the BDC-HFn solubility, stability, and ability to cross a blood-brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq.RESULTS: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model.CONCLUSIONS: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.
AB - BACKGROUND: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn).METHODS: We tested the BDC-HFn solubility, stability, and ability to cross a blood-brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq.RESULTS: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model.CONCLUSIONS: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.
KW - Alzheimer Disease/drug therapy
KW - Apoferritins
KW - Diarylheptanoids
KW - Endothelial Cells/metabolism
KW - Humans
KW - Inflammation/drug therapy
U2 - 10.3390/ijms23169237
DO - 10.3390/ijms23169237
M3 - Article
C2 - 36012501
SN - 1422-0067
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 16
M1 - 9237
ER -