Polymeric Nanoparticles to Control the Differentiation of Neural Stem Cells in the Subventricular Zone of the Brain
Abstract
Herein, we report the use of retinoic acid-loaded polymeric nanoparticles as a potent tool to induce the neuronal differentiation of subventricular zone neural stem cells. The intracellular delivery of retinoic acid by the nanoparticles activated nuclear retinoic acid receptors, decreased stemness, and increased proneurogenic gene expression. Importantly, this work reports for the first time a nanoparticle formulation able to modulate in vivo the subventricular zone neurogenic niche. The work further compares the dynamics of initial stages of differentiation between SVZ cells treated with retinoic acid-loaded polymeric nanoparticles and solubilized retinoic acid. The nanoparticle formulation developed here may ultimately offer new perspectives to treat neurodegenerative diseases.
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In most cases, RA-containing formulations have been administered by stereotaxic and not intravenous injection.
“In most cases, the formulations have been administered by stereotaxic and not intravenous injection66.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [66]
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 [66]
The effect was mediated by an increase in transcription of the pro-neurogenic genes Ngn1 and Mash1.
“The effect was mediated by an increase in transcription of the pro-neurogenic genes Ngn1 and Mash144,66.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [66]
The nanoparticles had a higher effect on neuronal differentiation than solubilized RA both in vitro and in vivo.
“The nanoparticles had a higher effect on neuronal differentiation than solubilized RA both in vitro and in vivo44,66.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [66]
Several RA-polymer conjugates have been developed to release RA by hydrolytic cleavage of ester bonds, by enzymatic cleavage of amide bonds by proteases present in the targeted tissue, or by reducing environments such as the cell cytoplasm.
“For example, several RA-polymer conjugates have been developed to release RA by hydrolytic cleavage of ester bonds50,52, by enzymatic cleavage of amide bonds by proteases present in the targeted tissue28,65–67 or by reducing environments56 such as the cell cytoplasm.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [66]
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Subventricular zone astrocytes are neural stem cells in the adult mammalian brain
Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., & Alvarez-Buylla, A. (1999) · Cell · doi:10.1016/s0092-8674(00)80783-7 · Cited by 3,898 · see citing works
Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398 · see citing works
Direct conversion of fibroblasts to functional neurons by defined factors
Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C., & Wernig, M. (2010) · Nature · doi:10.1038/nature08797 · Cited by 3,017 · see citing works
Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions
Ming, G.-L., & Song, H. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.001 · Cited by 2,651 · see citing works
Active Genes Are Tri-Methylated at K4 of Histone H3
Santos-Rosa, H., Schneider, R., Bannister, A. J., Sherriff, J., Bernstein, B. E., Emre, N. C. T., Schreiber, S. L., Mellor, J., & Kouzarides, T. (2002) · Nature · doi:10.1038/nature01080 · Cited by 2,138 · see citing works
EGF Converts Transit-Amplifying Neurogenic Precursors in the Adult Brain into Multipotent Stem Cells
Doetsch, F. K., Petreanu, L., Caillé, I., García‐Verdugo, J. M., & Álvarez-Buylla, A. (2002) · Neuron · doi:10.1016/s0896-6273(02)01133-9 · Cited by 1,048 · see citing works
Retinoic acid in the development, regeneration and maintenance of the nervous system
Maden, M. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2212 · Cited by 896 · see citing works
Corridors of migrating neurons in the human brain and their decline during infancy
Sanai, N., Nguyen, T., Ihrie, R. A., Mirzadeh, Z., Tsai, H.-H., Wong, M., Gupta, N., Berger, M. S., Huang, E., Garcia-Verdugo, J.-M., et al. (2011) · Nature · doi:10.1038/nature10487 · Cited by 849 · see citing works
Nuclear retinoid receptors and the transcription of retinoid-target genes
Bastien, J., & Rochette-Egly, C. (2004) · Gene · doi:10.1016/j.gene.2003.12.005 · Cited by 773 · see citing works
Regeneration of a germinal layer in the adult mammalian brain
Doetsch, F. K., García‐Verdugo, J. M., & Álvarez-Buylla, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11619 · Cited by 662 · see citing works
Basic helix-loop-helix factors in cortical development.
Ross, S. E., Greenberg, M., & Stiles, C. (2003) · Neuron · doi:10.1016/s0896-6273(03)00365-9 · Cited by 637 · see citing works
Bharali, D. J., Klejbor, I., Stachowiak, E. K., Dutta, P., Roy, I., Kaur, N., Bergey, E. J., Prasad, P. N., & Stachowiak, M. K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504926102 · Cited by 622 · see citing works
Kastner, P., Mark, M. P., Ghyselinck, N. B., Krężel, W., Dupé, V., Grondona, J. M., & Chambon, P. (1997) · Development · doi:10.1242/dev.124.2.313 · Cited by 429 · see citing works
Takahashi, J. B., Palmer, T. D., & Gage, F. H. (1999) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199901)38:1 · Cited by 412 · see citing works
Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells
Lim, D., Huang, Y.-C., Swigut, T., Mirick, A. L., García-Verdugo, J., Wysocka, J., Ernst, P., & Álvarez-Buylla, A. (2009) · Nature · doi:10.1038/nature07726 · Cited by 400 · see citing works
Pastrana, É., Cheng, L.-C., & Doetsch, F. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810407106 · Cited by 381 · see citing works
Shen, Q., Zhong, W., Jan, Y. N., & Temple, S. (2002) · Development · doi:10.1242/dev.129.20.4843 · Cited by 361 · see citing works
Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres
Suslov, O. N., Kukekov, V. G., Ignatova, T. N., & Steindler, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212525299 · Cited by 339 · see citing works
Gao, X., Tao, W., Lü, W., Zhang, Q., Zhang, Y., Jiang, X., & Fu, S. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.01.038 · Cited by 295 · see citing works
Dilworth, F. J., & Chambon, P. (2001) · Oncogene · doi:10.1038/sj.onc.1204329 · Cited by 269 · see citing works
Kim, E. J., Ables, J. L., Dickel, L. K., Eisch, A. J., & Johnson, J. E. B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018472 · Cited by 253 · see citing works
The Blood–Cerebrospinal Fluid Barrier: Structure and Functional Significance
Johanson, C. E., Stopa, E. G., & McMillan, P. N. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-938-3_4 · Cited by 249 · see citing works
SOX2 functions in adult neural stem cells
Episkopou, V. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.03.003 · Cited by 242 · see citing works
Differential expression of retinoid receptors in the adult mouse central nervous system
Krężel, W., Kastner, P., & Chambon, P. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00342-x · Cited by 238 · see citing works
Solubility of retinoids in water
Szuts, E. Z., & Harosi, F. I. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90482-x · Cited by 223 · see citing works
Bernardino, L., Agasse, F., Silva, B., Ferreira, R., Grade, S., & Malva, J. O. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0914 · Cited by 220 · see citing works
Self-citationImaging stem-cell-driven regeneration in mammals
Schroeder, T. (2008) · Nature · doi:10.1038/nature07043 · Cited by 205 · see citing works
Kim, E. J., Leung, C. T., Reed, R. R., & Johnson, J. E. B. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3178-07.2007 · Cited by 163 · see citing works
Activated c-Jun N-Terminal Kinase Is Required for Axon Formation
Oliva, A. A., Atkins, C. M., Copenagle, L., & Banker, G. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2625-06.2006 · Cited by 159 · see citing works
Nerve growth factor acts via retinoic acid synthesis to stimulate neurite outgrowth
Corcoran, J. P. T., & Maden, M. (1999) · Nature Neuroscience · doi:10.1038/7214 · Cited by 137 · see citing works
Bonnet, É., Touyarot, K., Alfos, S., Pallet, V., Higueret, P., & Abrous, D. N. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003487 · Cited by 129 · see citing works
Stavridis, M. P., Collins, B. J., & Storey, K. G. (2010) · Development · doi:10.1242/dev.043117 · Cited by 124 · see citing works
Germain, P., Gaudon, C., Pogenberg, V., Cianférani, S., DORSSELAER, A. V., Royer, C. A., Lazar, M. A., Bourguet, W., & Gronemeyer, H. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.03.008 · Cited by 121 · see citing works
Maia, J., Santos, T., Aday, S., Agasse, F., Cortes, L., Malva, J. O., Bernardino, L., & Ferreira, L. (2011) · ACS Nano · doi:10.1021/nn101724r · Cited by 99 · see citing works
Self-citationNeuropeptide Y Promotes Neurogenesis in Murine Subventricular Zone
Agasse, F., Bernardino, L. I., Kristiansen, H., Christiansen, S. H., Ferreira, R., Silva, B., Grade, S., Woldbye, D. P. D., & Malva, J. O. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0056 · Cited by 98 · see citing works
Self-citationRegulation of mouse embryonic stem cell neural differentiation by retinoic acid
Kim, M., Habiba, A., Doherty, J. M., Mills, J. C., Mercer, R. W., & Huettner, J. E. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.02.001 · Cited by 94 · see citing works
Wang, T., Zhang, H., & Parent, J. M. (2005) · Development · doi:10.1242/dev.01867 · Cited by 93 · see citing works
Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles
Kubek, M. J., Domb, A. J., & Veronesi, M. C. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.02.001 · Cited by 79 · see citing works
Jarvis, C. I., Goncalves, M. B. C. V., Clarke, E. E., Dogruel, M., Kalindjian, S. B., Thomas, S. A., Maden, M., & Corcoran, J. P. T. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07426.x · Cited by 78 · see citing works
Oishi, K., Watatani, K., Itoh, Y., Okano, H., Guillemot, F., Nakajima, K., & Gotoh, Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808400106 · Cited by 75 · see citing works
Modular patterning of structure and function of the striatum by retinoid receptor signaling
Liao, W.-L., Tsai, H., Wang, H., Chang, J., Lu, K.-M., Wu, H.-L., Lee, Y., Tsai, T., Takahashi, H., Wagner, M. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802109105 · Cited by 72 · see citing works
Spatiotemporal Fate Map of Neurogenin1 (Neurog1) Lineages in the Mouse Central Nervous System
Kim, E. J., Hori, K., Wyckoff, A., Dickel, L. K., Koundakjian, E., Goodrich, L., & Johnson, J. E. (2011) · The Journal of comparative neurology · doi:10.1002/cne.22574 · Cited by 66 · see citing works
Lü, J., Tan, L., Li, P., Gao, H., Fang, B., Ye, S., Geng, Z., Zheng, P., & Song, H. (2009) · BMC Cell Biology · doi:10.1186/1471-2121-10-57 · Cited by 64 · see citing works
Plane, J. M., Whitney, J. T., Schallert, T., & Parent, J. M. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.08.006 · Cited by 59 · see citing works
Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice
Lundell, T. G., Zhou, Q., & Doughty, M. L. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22165 · Cited by 54 · see citing works
Ascl1/Mash1 Is a Novel Target of Gli2 during Gli2-Induced Neurogenesis in P19 EC Cells
Voronova, A., Anna, F., Ryan, T. L., Madhoun, A. S. A., & Skerjanc, I. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019174 · Cited by 50 · see citing works
Agasse, F., Bernardino, L. I., Silva, B., Ferreira, R., Grade, S., & Malva, J. O. (2008) · Rejuvenation Research · doi:10.1089/rej.2007.0600 · Cited by 40 · see citing works
Self-citationLiu, X. S., Zhang, Z., Zhang, R. L., Gregg, S. R., Meng, H., & Chopp, M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.056 · Cited by 38 · see citing works
Nanomedicine boosts neurogenesis: new strategies for brain repair
Santos, T., Maia, J., Agasse, F., Xapelli, S., Ferreira, L., & Bernardino, L. I. (2012) · Integrative Biology · doi:10.1039/c2ib20129a · Cited by 30 · see citing works
Self-citationWu, M., Zhang, Y., Wu, N., et al. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22122 · Cited by 29 · see citing works
Hádinger, N., Varga, B. V., Berzsenyi, S., et al. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.02.004 · Cited by 28 · see citing works
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(2013) · Thieme eBooks · doi:10.1055/b-0034-92790 · Cited by 11 · see citing works
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Self-citation
- Authors
- Santos, T., Ferreira, R., Maia, J., Agasse, F., Xapelli, S., Cortes, L., Bragança, J., Malva, J. O., Ferreira, L., & Bernardino, L.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- Biocant – Associação de Transferência de Tecnologia (PT)
- University of Algarve (PT)
- University of Beira Interior (PT)
- Corresponding author
- Ferreira, Lino
- Bernardino, Liliana
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-11-29
- Volume
- 6
- Issue
- 12
- Pages
- 10463-10474
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2030676812
- Cited by
- 92
- References
- 53
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 12 · 2017: 12 · 2016: 13 · 2015: 11 · 2014: 6 · 2013: 3
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- polymeric nanoparticles, retinoic acid, neural stem cells, subventricular zone, neuronal differentiation, retinoic acid receptor, intracellular drug delivery, neurogenic niche, stemness, neurodegenerative diseases
- MeSH terms
- Animals, Axons, Cell Differentiation, Cell Nucleus, Drug Carriers, Gene Expression Regulation, Nerve Tissue Proteins, Neurons, Polyethyleneimine, Tretinoin, Receptors, Retinoic Acid, Lateral Ventricles, Mice, Basic Helix-Loop-Helix Proteins, Nanoparticles, Neural Stem Cells
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