Advances in anti-Alzheimer’s disease nano drug delivery system based on pathogenic mechanism of ferroptosis

SU Haiying; WANG Yukun; LI Weisong; ZHOU Jianping; CHENG Hao

doi:10.11665/j.issn.1000-5048.2024040702

Journal of China Pharmaceutical University > 2024 > 55(5): 613-623. > DOI: 10.11665/j.issn.1000-5048.2024040702

SU Haiying, WANG Yukun, LI Weisong, et al. Advances in anti-Alzheimer’s disease nano drug delivery system based on pathogenic mechanism of ferroptosis[J]. J China Pharm Univ, 2024, 55(5): 613 − 623. DOI: 10.11665/j.issn.1000-5048.2024040702

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Advances in anti-Alzheimer’s disease nano drug delivery system based on pathogenic mechanism of ferroptosis

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82404565); and China Postdoctoral Science Foundation (2023M733892)

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Received Date: April 06, 2024

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Abstract

Abstract

Ferroptosis, a programmed cell death induced by iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species, is a key pathological mechanism of neuronal death during the progression of Alzheimer’s disease (AD), contributing to the formation of “Ferroptosis Hypothesis” for AD pathogenesis. In recent years, there has been extensive research on therapeutic strategies for AD based on the pathogenic mechanism of ferroptosis, focusing primarily on the dysregulation of brain iron metabolism and redox regulation in microenvironment. However, presence of blood-brain barrier and intricate pathological environment within brain impose limitations on intracranial drug transportation, distribution and therapeutic efficacy, thereby necessitating advancements in drug delivery technology. Based on description of ferroptosis process and its regulatory mechanisms, this review explores the association between iron overload and redox imbalance with neuronal loss and AD development, and additionally, summarizes the advancements in nano drug delivery systems targeting iron overload and redox imbalance for potential anti-AD treatments, so as to offer some novel perspectives for AD treatment and drug development.
- Alzheimer’s disease,
- neuronal ferroptosis,
- nano drug delivery system,
- iron homeostasis regulation,
- redox regulation

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References

[1]	Wang YQ, Jia RX, Liang JH, et al. Dementia in China (2015-2050) estimated using the 1% population sampling survey in 2015[J]. Geriatr Gerontol Int, 2019, 19(11): 1096-1100. doi: 10.1111/ggi.13778
[2]	Ayton S, Portbury S, Kalinowski P, et al. Regional brain iron associated with deterioration in Alzheimer’s disease: a large cohort study and theoretical significance[J]. Alzheimers Dement, 2021, 17(7): 1244-1256. doi: 10.1002/alz.12282
[3]	Yan N, Zhang JJ. Iron metabolism, ferroptosis, and the links with Alzheimer’s disease[J]. Front Neurosci, 2020, 13: 1443. doi: 10.3389/fnins.2019.01443
[4]	Greenough MA, Lane DJR, Balez R, et al. Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations[J]. Cell Death Differ, 2022, 29(11): 2123-2136. doi: 10.1038/s41418-022-01003-1
[5]	Liu G, Men P, Kudo W, et al. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease[J]. Neurosci Lett, 2009, 455(3): 187-190. doi: 10.1016/j.neulet.2009.03.064
[6]	Naidu SAG, Wallace TC, Davies KJA, et al. Lactoferrin for mental health: neuro-redox regulation and neuroprotective effects across the blood-brain barrier with special reference to neuro-COVID-19[J]. J Diet Suppl, 2023, 20(2): 218-253. doi: 10.1080/19390211.2021.1922567
[7]	Kamalinia G, Khodagholi F, Atyabi F, et al. Enhanced brain delivery of deferasirox-lactoferrin conjugates for iron chelation therapy in neurodegenerative disorders: in vitro and in vivo studies[J]. Mol Pharm, 2013, 10(12): 4418-4431. doi: 10.1021/mp4002014
[8]	Akilo OD, Kumar P, Choonara YE, et al. Hypothesis: apo-lactoferrin-Galantamine Proteo-alkaloid Conjugate for Alzheimer’s disease Intervention[J]. J Cell Mol Med, 2018, 22(3): 1957-1963. doi: 10.1111/jcmm.13484
[9]	Shi P, Li M, Ren JS, et al. Gold nanocage-based dual responsive “caged metal Chelator” release system: noninvasive remote control with near infrared for potential treatment of Alzheimer’s disease[J]. Adv Funct Mater, 2013, 23(43): 5412-5419. doi: 10.1002/adfm.201301015
[10]	Li LH, Tan LW, Zhang Q, et al. Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: characterization, neuroprotective effect and in vivo pharmacokinetic study[J]. Front Bioeng Biotechnol, 2023, 11: 1168408. doi: 10.3389/fbioe.2023.1168408
[11]	Du F, Qian ZM, Luo QQ, et al. Hepcidin suppresses brain iron accumulation by downregulating iron transport proteins in iron-overloaded rats[J]. Mol Neurobiol, 2015, 52(1): 101-114. doi: 10.1007/s12035-014-8847-x
[12]	Xu Y, Zhang YT, Zhang JH, et al. Astrocyte hepcidin ameliorates neuronal loss through attenuating brain iron deposition and oxidative stress in APP/PS1 mice[J]. Free Radic Biol Med, 2020, 158: 84-95. doi: 10.1016/j.freeradbiomed.2020.07.012
[13]	Bayele HK, Balesaria S, Srai SK. Phytoestrogens modulate hepcidin expression by Nrf2: implications for dietary control of iron absorption[J]. Free Radic Biol Med, 2015, 89: 1192-1202. doi: 10.1016/j.freeradbiomed.2015.11.001
[14]	Pinheiro RGR, Granja A, Loureiro JA, et al. Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer’s disease[J]. Eur J Pharm Sci, 2020, 148: 105314. doi: 10.1016/j.ejps.2020.105314
[15]	Shen Y, Cao B, Snyder NR, et al. ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood-brain barrier[J]. J Nanobiotechnology, 2018, 16(1): 13. doi: 10.1186/s12951-018-0340-7
[16]	Sun YY, Xia XH, Basnet D, et al. Mechanisms of ferroptosis and emerging links to the pathology of neurodegenerative diseases[J]. Front Aging Neurosci, 2022, 14: 904152. doi: 10.3389/fnagi.2022.904152
[17]	Karthika C, Appu AP, Akter R, et al. Potential innovation against Alzheimer’s disorder: a tricomponent combination of natural antioxidants (vitamin E, quercetin, and basil oil) and the development of its intranasal delivery[J]. Environ Sci Pollut Res Int, 2022, 29(8): 10950-10965. doi: 10.1007/s11356-021-17830-7
[18]	Singh A, Rakshit D, Kumar A, et al. Vitamin E modified polyamidoamine dendrimer for piperine delivery to alleviate Aβ_1-42 induced neurotoxicity in BALB/c mice model[J]. J Biomater Sci Polym Ed, 2023, 34(16): 2232-2254. doi: 10.1080/09205063.2023.2230857
[19]	Kaboli Z, Hosseini MJ, Sadighian S, et al. Valine conjugated polymeric nanocarriers for targeted co-delivery of rivastigmine and quercetin in rat model of Alzheimer disease[J]. Int J Pharm, 2023, 645: 123418. doi: 10.1016/j.ijpharm.2023.123418
[20]	Aliakbari F, Shabani AA, Bardania H, et al. Formulation and anti-neurotoxic activity of baicalein-incorporating neutral nanoliposome[J]. Colloids Surf B Biointerfaces, 2018, 161: 578-587. doi: 10.1016/j.colsurfb.2017.11.023
[21]	Haddad M, Hervé V, Ben Khedher MR, et al. Glutathione: an old and small molecule with great functions and new applications in the brain and in Alzheimer’s disease[J]. Antioxid Redox Signal, 2021, 35(4): 270-292. doi: 10.1089/ars.2020.8129
[22]	Paka GD, Ramassamy C. Optimization of curcumin-loaded PEG-PLGA nanoparticles by GSH functionalization: investigation of the internalization pathway in neuronal cells[J]. Mol Pharm, 2017, 14(1): 93-106. doi: 10.1021/acs.molpharmaceut.6b00738
[23]	Wu LY, Xian XH, Tan ZX, et al. The role of iron metabolism, lipid metabolism, and redox homeostasis in Alzheimer’s disease: from the perspective of ferroptosis[J]. Mol Neurobiol, 2023, 60(5): 2832-2850. doi: 10.1007/s12035-023-03245-7
[24]	Kulkarni P, Rawtani D, Barot T. Design, development and in-vitro/in-vivo evaluation of intranasally delivered Rivastigmine and N-Acetyl Cysteine loaded bifunctional niosomes for applications in combinative treatment of Alzheimer’s disease[J]. Eur J Pharm Biopharm, 2021, 163: 1-15. doi: 10.1016/j.ejpb.2021.02.015
[25]	Eleftheriadou D, Kesidou D, Moura F, et al. Redox-responsive nanobiomaterials-based therapeutics for neurodegenerative diseases[J]. Small, 2020, 16(43): e1907308. doi: 10.1002/smll.201907308
[26]	Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis[J]. Cell, 2018, 172(3): 409-422. e21.
[27]	Vivash L, Malpas CB, Meletis C, et al. A phase 1b open-label study of sodium selenate as a disease-modifying treatment for possible behavioral variant frontotemporal dementia[J]. Alzheimers Dement, 2022, 8(1): e12299.
[28]	Qi YJ, Yi PJ, He T, et al. Quercetin-loaded selenium nanoparticles inhibit amyloid-β aggregation and exhibit antioxidant activity[J]. Colloids Surf A Physicochem Eng Aspects, 2020, 602: 125058. doi: 10.1016/j.colsurfa.2020.125058
[29]	Wang JY, Wang ZK, Li YQ, et al. Blood brain barrier-targeted delivery of double selenium nanospheres ameliorates neural ferroptosis in Alzheimer’s disease[J]. Biomaterials, 2023, 302: 122359. doi: 10.1016/j.biomaterials.2023.122359
[30]	Alim I, Caulfield JT, Chen YX, et al. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke[J]. Cell, 2019, 177(5): 1262-1279. e25.
[31]	Chen J, Ou ZJ, Gao TT, et al. Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy[J]. Biomedecine Pharmacother, 2022, 156: 113953. doi: 10.1016/j.biopha.2022.113953
[32]	Shao L, Dong C, Geng DQ, et al. Ginkgolide B protects against cognitive impairment in senescence-accelerated P8 mice by mitigating oxidative stress, inflammation and ferroptosis[J]. Biochem Biophys Res Commun, 2021, 572: 7-14. doi: 10.1016/j.bbrc.2021.07.081
[33]	Yang PF, Cai XL, Zhou K, et al. A novel oil-body nanoemulsion formulation of ginkgolide B: pharmacokinetics study and in vivo pharmacodynamics evaluations[J]. J Pharm Sci, 2014, 103(4): 1075-1084. doi: 10.1002/jps.23866
[34]	Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme Q₁₀ supplementation: efficacy, safety, and formulation challenges[J]. Compr Rev Food Sci Food Saf, 2020, 19(2): 574-594. doi: 10.1111/1541-4337.12539
[35]	Wear D, Vegh C, Sandhu JK, et al. Ubisol-Q₁₀, a nanomicellar and water-dispersible formulation of coenzyme-Q₁₀ as a potential treatment for Alzheimer’s and Parkinson’s disease[J]. Antioxidants, 2021, 10(5): 764. doi: 10.3390/antiox10050764
[36]	Muthukumaran K, Kanwar A, Vegh C, et al. Ubisol-Q₁₀ (a nanomicellar water-soluble formulation of CoQ₁₀) treatment inhibits alzheimer-type behavioral and pathological symptoms in a double transgenic mouse (TgAPEswe, PSEN1dE9) model of Alzheimer’s disease[J]. J Alzheimers Dis, 2018, 61(1): 221-236.
[37]	Yang P, Sheng DY, Guo Q, et al. Neuronal mitochondria-targeted micelles relieving oxidative stress for delayed progression of Alzheimer’s disease[J]. Biomaterials, 2020, 238: 119844. doi: 10.1016/j.biomaterials.2020.119844
[38]	Han Y, Chu XY, Cui L, et al. Neuronal mitochondria-targeted therapy for Alzheimer’s disease by systemic delivery of resveratrol using dual-modified novel biomimetic nanosystems[J]. Drug Deliv, 2020, 27(1): 502-518. doi: 10.1080/10717544.2020.1745328

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Advances in anti-Alzheimer’s disease nano drug delivery system based on pathogenic mechanism of ferroptosis

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