Design of Red Fluorescence Ce-Based Carbon Dots of High and Balanced Multiple Functions against Alzheimer’s β-Amyloid Fibrillization
Abstract
The intricate pathophysiology of Alzheimer’s disease (AD), characterized by β-amyloid (Aβ) deposition, oxidative stress, and neuroinflammation, presents significant challenges for conventional single-target therapeutic approaches, thereby necessitating the development of innovative multifunctional theranostic strategies. Herein, red fluorescence cerium-based carbon dots (CCP-CD) were designed and synthesized via a one-step solvothermal method by purposely selecting curcumin (Cur) for inhibitory and anti-inflammatory effects, Ce(NO 3 ) 3 ·6H 2 O for enhancing antioxidant activity, and p-phenylenediamine (p-PD) for modulating fluorescence property as precursors. The as-prepared CCP-CD potently suppressed Aβ fibrillization and strongly eliminated multiple reactive oxygen species (ROS) (·OH, O 2 ·–, DPPH·) at low concentrations (1–10 μg/mL). Moreover, CCP-CD facilitates detection of Aβ plaques through a turn-on red fluorescence mechanism for both in vitro and in vivo imaging and quantification. In vitro assays showed that CCP-CD markedly attenuated Aβ-induced cytotoxicity and increased cell viability from ∼60 to 95%, as well as exhibited excellent anti-inflammatory effects by reducing the levels of TNF-α and IL-6 in BV-2 cells. In vivo experiments revealed that CCP-CD effectively suppressed Aβ plaque formation in the AD nematodes and prolonged the lifespan from 13 to 20 d. The unique structural characteristics of CCP-CD, including its conjugated aromatic framework, reversible Ce 3+ /Ce 4+ redox pair, and abundant O- and N-containing functional groups, facilitate balanced multiple therapeutic and diagnostic functions. The work has thus provided an exceptional nanoagent for detecting Aβ and fighting against Aβ-associated toxicities.
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Oxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants or immunosuppressants.
“Oxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants (CeNCs, tannic acid, curcumin, quercetin) or immunosuppressants (dexamethasone, cyclophosphamide) to prevent neuronal death and attenuate inflammation [58,70,71,78].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
Many carbon dots exhibit antioxidant activity.
“many CDs exhibit antioxidant activity [78,79,80]”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
In nematode models, a significant prolongation of lifespan upon administration of Nps is shown.
“In nematode models, a significant prolongation of lifespan upon the administration of Nps is shown [68,77,78,79,80,81].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
Many studies include an antioxidant component aimed at reducing ROS and an anti-inflammatory effect via delivery of immunosuppressants.
“Many studies also include an antioxidant component aimed at reducing the level of ROS [64,72,78,80,83], and an anti-inflammatory effect, implemented through the delivery of immunosuppressants [70,71].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
The effectiveness of therapy is confirmed in most studies on cellular models, where a significant increase in survival of neuronal cells upon exposure to toxic concentrations of Aβ is shown.
“The effectiveness of therapy is confirmed in most studies on cellular models, where a significant increase in the survival of neuronal cells upon exposure to toxic concentrations of Aβ is shown [29,64,72,76,77,78,80,83].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
CDs and triggerable-release systems appear particularly promising for further development, as they address two key challenges: CDs combine intrinsic fluorescence with therapeutic activity in a single ultrasmall particle, while triggerable-release systems enable on-demand therapy activation using pathological signals, mitigating dose and pharmacokinetic conflicts.
“Among the platforms surveyed, CDs [78,79] and triggerable-release systems [83] appear particularly promising for further development, as they address two key challenges identified in our analysis: CDs combine intrinsic fluorescence with therapeutic activity in a single ultrasmall particle (bypassing the need for additional diagnostic labels), while triggerable-release systems enable on-demand ther”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
CD-based platforms exemplify parallel function combinations rather than true synergy, as their imaging and therapeutic capabilities operate independently without mutual enhancement.
“Upon closer examination, CD-based platforms [77,78,79,80] exemplify parallel function combinations rather than true synergy, as their imaging and therapeutic capabilities operate independently without mutual enhancement.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [78]
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- Authors
- Wei, Z., Dong, X., & Sun, Y.
- Affiliations
- Ministry of Education of the People's Republic of China (CN)
- Corresponding author
- Dong, Xiaoyan
- Sun, Yan
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-08-20
- Volume
- 17
- Issue
- 35
- Pages
- 49737-49750
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W4413342757
- Cited by
- 5
- References
- 60
- Citations by year
- 2026: 5
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (22178259)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Carbon and Quantum Dots Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Materials Science › Materials Chemistry › Advanced Nanomaterials in Catalysis
- Keywords
- red fluorescence, Alzheimer's disease, theranostics, curcumin, p-phenylenediamine, reactive oxygen species scavenging, anti-inflammatory activity, oxidative stress, neuroinflammation, Caenorhabditis elegans
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Antioxidants, Carbon, Cell Line, Cell Survival, Cerium, Curcumin, Fluorescence, Humans, Amyloid beta-Peptides, Caenorhabditis elegans, Reactive Oxygen Species, Quantum Dots, Mice
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