Potential Alzheimer's Disease Therapeutic Nano-platform: Discovery of Amyloid-beta Plaque Disaggregating Agent and Brain-targeted Delivery System Using Porous Silicon Nanoparticles

Overview

Journal Bioact Mater

Specialty Biomedical Engineering

Date 2023 Jan 23

PMID 36685808

Authors

Jaehoon Kim

Hyeji Um

Na Hee Kim

Dokyoung Kim

Affiliations

Soon will be listed here.

Abstract

There has been a lot of basic and clinical research on Alzheimer's disease (AD) over the last 100 years, but its mechanisms and treatments have not been fully clarified. Despite some controversies, the amyloid-beta hypothesis is one of the most widely accepted causes of AD. In this study, we disclose a new amyloid-beta plaque disaggregating agent and an AD brain-targeted delivery system using porous silicon nanoparticles (pSiNPs) as a therapeutic nano-platform to overcome AD. We hypothesized that the negatively charged sulfonic acid functional group could disaggregate plaques and construct a chemical library. As a result of the in vitro assay of amyloid plaques and library screening, we confirmed that 6-amino-2-naphthalenesulfonic acid (ANA) showed the highest efficacy for plaque disaggregation as a hit compound. To confirm the targeted delivery of ANA to the AD brain, a nano-platform was created using porous silicon nanoparticles (pSiNPs) with ANA loaded into the pore of pSiNPs and biotin-polyethylene glycol (PEG) surface functionalization. The resulting nano-formulation, named Biotin-CaCl2-ANA-pSiNPs (BCAP), delivered a large amount of ANA to the AD brain and ameliorated memory impairment of the AD mouse model through the disaggregation of amyloid plaques in the brain. This study presents a new bioactive small molecule for amyloid plaque disaggregation and its promising therapeutic nano-platform for AD brain-targeted delivery.

Citing Articles

Nanoscale drug formulations for the treatment of Alzheimer's disease progression.

Liu L, He H, Du B, He Y RSC Adv. 2025; 15(6):4031-4078.

PMID: 39926227 PMC: 11803502. DOI: 10.1039/d4ra08128e.

Neuroprotective Potential of Indole-Based Compounds: A Biochemical Study on Antioxidant Properties and Amyloid Disaggregation in Neuroblastoma Cells.

Ciaglia T, Miranda M, Di Micco S, Vietri M, Smaldone G, Musella S Antioxidants (Basel). 2025; 13(12.

PMID: 39765912 PMC: 11673510. DOI: 10.3390/antiox13121585.

Nanocarrier-mediated siRNA delivery: a new approach for the treatment of traumatic brain injury-related Alzheimer's disease.

Jin J, Zhang H, Lu Q, Tian L, Yao S, Lai F Neural Regen Res. 2024; 20(9):2538-2555.

PMID: 39314170 PMC: 11801294. DOI: 10.4103/NRR.NRR-D-24-00303.

Triptolide activates the Nrf2 signaling pathway and inhibits the NF-κB signaling pathway to improve Alzheimer disease.

He Z, Botchway B, Zhang Y, Liu X Metab Brain Dis. 2023; 39(1):173-182.

PMID: 37624431 DOI: 10.1007/s11011-023-01278-4.

Bacteria associated with glioma: a next wave in cancer treatment.

Meng Y, Sun J, Zhang G, Yu T, Piao H Front Cell Infect Microbiol. 2023; 13:1164654.

PMID: 37201117 PMC: 10185885. DOI: 10.3389/fcimb.2023.1164654.

References

Vaz M, Silvestre S . Alzheimer's disease: Recent treatment strategies. Eur J Pharmacol. 2020; 887:173554. DOI: 10.1016/j.ejphar.2020.173554. View

Balasubramanian V, Domanskyi A, Renko J, Sarparanta M, Wang C, Correia A . Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke. Biomaterials. 2019; 227:119556. DOI: 10.1016/j.biomaterials.2019.119556. View

Santos H, Riikonen J, Salonen J, Makila E, Heikkila T, Laaksonen T . In vitro cytotoxicity of porous silicon microparticles: effect of the particle concentration, surface chemistry and size. Acta Biomater. 2009; 6(7):2721-31. DOI: 10.1016/j.actbio.2009.12.043. View

Snow A, Cummings J, Tanzi R, Lake T . In vitro comparison of major memory-support dietary supplements for their effectiveness in reduction/inhibition of beta-amyloid protein fibrils and tau protein tangles: key primary targets for memory loss. Sci Rep. 2021; 11(1):3001. PMC: 7884837. DOI: 10.1038/s41598-020-79275-1. View

Hampel H, Hardy J, Blennow K, Chen C, Perry G, Kim S . The Amyloid-β Pathway in Alzheimer's Disease. Mol Psychiatry. 2021; 26(10):5481-5503. PMC: 8758495. DOI: 10.1038/s41380-021-01249-0. View

Park J, Gu L, von Maltzahn G, Ruoslahti E, Bhatia S, Sailor M . Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009; 8(4):331-6. PMC: 3058936. DOI: 10.1038/nmat2398. View

Henstridge C, Hyman B, Spires-Jones T . Beyond the neuron-cellular interactions early in Alzheimer disease pathogenesis. Nat Rev Neurosci. 2019; 20(2):94-108. PMC: 6545070. DOI: 10.1038/s41583-018-0113-1. View

Kim D, Baik S, Kang S, Cho S, Bae J, Cha M . Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer's Disease in Mice, Observed by Two-Photon Imaging. ACS Cent Sci. 2017; 2(12):967-975. PMC: 5200925. DOI: 10.1021/acscentsci.6b00309. View

Walker F . Huntington's disease. Lancet. 2007; 369(9557):218-28. DOI: 10.1016/S0140-6736(07)60111-1. View

10.

Liu P, Xie Y, Meng X, Kang J . History and progress of hypotheses and clinical trials for Alzheimer's disease. Signal Transduct Target Ther. 2019; 4:29. PMC: 6799833. DOI: 10.1038/s41392-019-0063-8. View

11.

Pinheiro R, Coutinho A, Pinheiro M, Neves A . Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?. Int J Mol Sci. 2021; 22(21). PMC: 8584083. DOI: 10.3390/ijms222111654. View

12.

Wohlfart S, Gelperina S, Kreuter J . Transport of drugs across the blood-brain barrier by nanoparticles. J Control Release. 2011; 161(2):264-73. DOI: 10.1016/j.jconrel.2011.08.017. View

13.

Kealy J, Greene C, Campbell M . Blood-brain barrier regulation in psychiatric disorders. Neurosci Lett. 2018; 726:133664. DOI: 10.1016/j.neulet.2018.06.033. View

14.

Ferrao-Gonzales A, Robbs B, Moreau V, Ferreira A, Juliano L, Valente A . Controlling {beta}-amyloid oligomerization by the use of naphthalene sulfonates: trapping low molecular weight oligomeric species. J Biol Chem. 2005; 280(41):34747-54. DOI: 10.1074/jbc.M501651200. View

15.

Kim J, Seo Y, Kim J, Goo N, Jeong Y, Bae H . Casticin ameliorates scopolamine-induced cognitive dysfunction in mice. J Ethnopharmacol. 2020; 259:112843. DOI: 10.1016/j.jep.2020.112843. View

16.

Yun Kim H, Lee D, Chung B, Kim H, Kim Y . Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits. J Vis Exp. 2016; (109). PMC: 4829024. DOI: 10.3791/53308. View

17.

Purushothaman B, Lee J, Hong S, Song J . Multifunctional TPP-PEG-biotin self-assembled nanoparticle drug delivery-based combination therapeutic approach for co-targeting of GRP78 and lysosome. J Nanobiotechnology. 2020; 18(1):102. PMC: 7372800. DOI: 10.1186/s12951-020-00661-y. View

18.

Luo M, Lewik G, Ratcliffe J, Choi C, Makila E, Tong W . Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma. ACS Appl Mater Interfaces. 2019; 11(37):33637-33649. DOI: 10.1021/acsami.9b10787. View

19.

Wang H, Pevsner J . Detection of endogenous biotin in various tissues: novel functions in the hippocampus and implications for its use in avidin-biotin technology. Cell Tissue Res. 1999; 296(3):511-6. DOI: 10.1007/s004410051311. View

20.

van Dyck C . Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise. Biol Psychiatry. 2017; 83(4):311-319. PMC: 5767539. DOI: 10.1016/j.biopsych.2017.08.010. View