Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles
Open accessAbstract
Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RARα) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in β-catenin activation and neuronal differentiation, and increased RARα levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies.Statement of significance Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RARα) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies.
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Light-activatable nanoparticles containing RA that disassemble in minutes after activation by a blue laser at 405 nm have been prepared.
“In that sense, light-activatable nanoparticles containing RA that disassemble in minutes after activation by a blue laser at 405 nm have been prepared25,26,60.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
Formulations with high (above 100 μg/mg), medium (between 100 and 25 μg/mg), and low (below 25 μg/mg) RA loading have been described.
“Formulations with high (above 100 μg/mg of formulation)51,56,60, medium (between 100 and 25 μg/mg of formulation)44,45, and low (below 25 μg/mg of formulation)7,58 loading have been described.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
Light-activatable formulations presented higher activity than formulations in which RA was released by passive diffusion because they rapidly saturated nuclear receptors.
“Importantly, these formulations presented higher activity than formulations in which RA was released by passive diffusion (not light triggered) because they rapidly saturated nuclear receptors.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
Most preclinical tests were performed in mice in the context of regenerative medicine and cancer.
“Most preclinical tests were performed in mice in the context of regenerative medicine45,60,66,68 and cancer22,25,56.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
The combined action of blue light and RA enhanced endogenous neurogenesis.
“The combined action of blue light and RA enhanced endogenous neurogenesis.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
A single short pulse of light prompted β-catenin-dependent neuronal differentiation and RARα upregulation.
“A single short pulse of light prompted β-catenin-dependent neuronal differentiation and RARα upregulation.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [60]
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- Authors
- Santos, T., Ferreira, R., Quartin, E., Boto, C., Saraiva, C., Bragança, J., Peça, J., Rodrigues, C., Ferreira, L., & Bernardino, L.
- Affiliations
- University of Beira Interior (PT)
- Biocant – Associação de Transferência de Tecnologia (PT)
- University of Algarve (PT)
- Centro de Neurociências e Biologia Celular (PT)
- University of Lisbon (PT)
- Corresponding author
- Bernardino, Liliana
- ORCID
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 59
- Pages
- 293-302
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2731405015
- Cited by
- 26
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia
- Programa Operacional Temático Factores de Competitividade (FCOMP-01-0124-FEDER-041099, PTDC/SAU-NEU/104415/2008, SFRH/BD/79526/2011)
- European Research Council (007491, 307384, Centro-07-ST24-FEDER-002008, UID/Multi/00709)
- European Commission
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Laser Applications in Dentistry and Medicine
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- neurogenesis, retinoic acid, blue light, reactive oxygen species, NADPH oxidase, retinoic acid receptor alpha, β-catenin, neuronal differentiation, controlled drug release, brain regeneration
- MeSH terms
- Retinoic Acid Receptor alpha, Animals, Delayed-Action Preparations, Light, Tretinoin, Lateral Ventricles, Mice, Nanoparticles, Neurogenesis, Neural Stem Cells
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