Gold nanoparticle-assisted delivery of brain-derived neurotrophic factor to cerebral organoids
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Byumseok Koh1(
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Gold nanoparticle (AuNP)-assisted delivery of proteins/drugs to cells or in vivo systems has long been studied. However, their interaction with in vivo mimicking organoids is still largely unknown. Here, we conjugated brain-derived neurotropic factor (BDNF) to the AuNP surface and monitored how AuNP–BDNF interacts with cerebral organoids. Data suggest that AuNP–BDNF can successfully enter cerebral organoids and can be found up to 15.21 µm inside cerebral organoids. AuNP–BDNF does not induce significant cytotoxicity to cerebral organoids at concentrations up to 2 nM and increases the expression of 75 genes compared to control cerebral organoids. These data suggest the successful delivery of BDNF through AuNP–BDNF conjugation in cerebral organoids, and the conjugation can affect its differentiation.
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Gold nanoparticle-assisted delivery of brain-derived neurotrophic factor to cerebral organoids
), Byumseok Koh1(
)
Abstract
Gold nanoparticle (AuNP)-assisted delivery of proteins/drugs to cells or in vivo systems has long been studied. However, their interaction with in vivo mimicking organoids is still largely unknown. Here, we conjugated brain-derived neurotropic factor (BDNF) to the AuNP surface and monitored how AuNP–BDNF interacts with cerebral organoids. Data suggest that AuNP–BDNF can successfully enter cerebral organoids and can be found up to 15.21 µm inside cerebral organoids. AuNP–BDNF does not induce significant cytotoxicity to cerebral organoids at concentrations up to 2 nM and increases the expression of 75 genes compared to control cerebral organoids. These data suggest the successful delivery of BDNF through AuNP–BDNF conjugation in cerebral organoids, and the conjugation can affect its differentiation.
References(41)
Liu, J. Y.; Peng, Q. Protein-gold nanoparticle interactions and their possible impact on biomedical applications. Acta Biomater. 2017, 55, 13–27.
Rana, S.; Bajaj, A.; Mout, R.; Rotello, V. M. Monolayer coated gold nanoparticles for delivery applications. Adv. Drug Deliv. Rev. 2012, 64, 200–216.
Jeong, E. H.; Jung, G.; Hong, C. A.; Lee, H. Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications. Arch. Pharm. Res. 2014, 37, 53–59.
Almeida, J. P. M.; Lin, A. Y.; Figueroa, E. R.; Foster, A. E.; Drezek, R. A. In vivo gold nanoparticle delivery of peptide vaccine induces anti-tumor immune response in prophylactic and therapeutic tumor models. Small 2015, 11, 1453–1459.
Kim, C. K.; Ghosh, P.; Rotello, V. M. Multimodal drug delivery using gold nanoparticles. Nanoscale 2009, 1, 61–67.
Ryou, S. M.; Yeom, J. H.; Kang, H. J.; Won, M.; Kim, J. S.; Lee, B.; Seong, M. J.; Ha, N. C.; Bae, J.; Lee, K. Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins. J. Control. Release 2014, 196, 287–294.
Lee, C. S.; Kim, H.; Yu, J.; Yu, S. H.; Ban, S.; Oh, S.; Jeong, D.; Im, J.; Baek, M. J.; Kim, T. H. Doxorubicin-loaded oligonucleotide conjugated gold nanoparticles: A promising in vivo drug delivery system for colorectal cancer therapy. Eur. J. Med. Chem. 2017, 142, 416–423.
Mbatha, L. S.; Maiyo, F.; Daniels, A.; Singh, M. Dendrimer-coated gold nanoparticles for efficient folate-targeted mRNA delivery in vitro. Pharmaceutics 2021, 13, 900.
Lancaster, M. A.; Renner, M.; Martin, C. A.; Wenzel, D.; Bicknell, L. S.; Hurles, M. E.; Homfray, T.; Penninger, J. M.; Jackson, A. P.; Knoblich, J. A. Cerebral organoids model human brain development and microcephaly. Nature 2013, 501, 373–379.
Lancaster, M. A.; Corsini, N. S.; Wolfinger, S.; Gustafson, E. H.; Phillips, A. W.; Burkard, T. R.; Otani, T.; Livesey, F. J.; Knoblich, J. A. Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 2017, 35, 659–666.
Xiang, Y. F.; Tanaka, Y.; Patterson, B.; Kang, Y. J.; Govindaiah, G.; Roselaar, N.; Cakir, B.; Kim, K. Y.; Lombroso, A. P.; Hwang, S. M. et al. Fusion of regionally specified HPSC-derived organoids models human brain development and interneuron migration. Cell Stem Cell 2017, 21, 383–398.e7.
Amin, N. D.; Paşca, S. P. Building models of brain disorders with three-dimensional organoids. Neuron 2018, 100, 389–405.
Koo, B.; Choi, B.; Park, H.; Yoon, K. J. Past, present, and future of brain organoid technology. Mol. Cells 2019, 42, 617–627.
Mansour, A. A.; Gonçalves, J. T.; Bloyd, C. W.; Li, H.; Fernandes, S.; Quang, D.; Johnston, S.; Parylak, S. L.; Jin, X.; Gage, F. H. An in vivo model of functional and vascularized human brain organoids. Nat. Biotechnol. 2018, 36, 432–441.
Hodge, R. D.; Bakken, T. E.; Miller, J. A.; Smith, K. A.; Barkan, E. R.; Graybuck, L. T.; Close, J. L.; Long, B.; Johansen, N.; Penn, O. et al. Conserved cell types with divergent features in human versus mouse cortex. Nature 2019, 573, 61–68.
Pryluk, R.; Kfir, Y.; Gelbard-Sagiv, H.; Fried, I.; Paz, R. A tradeoff in the neural code across regions and species. Cell 2019, 176, 597–609.E18.
Gordon, A.; Yoon, S. J.; Tran, S. S.; Makinson, C. D.; Park, J. Y.; Andersen, J.; Valencia, A. M.; Horvath, S.; Xiao, X. S.; Huguenard, J. R. et al. Long-term maturation of human cortical organoids matches key early postnatal transitions. Nat. Neurosci. 2021, 24, 331–342.
Kim, H. M.; Lee, S. H.; Lim, J.; Yoo, J.; Hwang, D. Y. The epidermal growth factor receptor variant type III mutation frequently found in gliomas induces astrogenesis in human cerebral organoids. Cell Prolif. 2021, 54, e12965.
Groveman, B. R.; Ferreira, N. C.; Foliaki, S. T.; Walters, R. O.; Winkler, C. W.; Race, B.; Hughson, A. G.; Zanusso, G.; Haigh, C. L. Human cerebral organoids as a therapeutic drug screening model for creutzfeldt-jakob disease. Sci. Rep. 2021, 11, 5165.
Arzua, T.; Yan, Y. S.; Jiang, C. S.; Logan, S.; Allison, R. L.; Wells, C.; Kumar, S. N.; Schäfer, R.; Bai, X. W. Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids. Transl. Psychiatry 2020, 10, 347.
Farooq, M. U.; Novosad, V.; Rozhkova, E. A.; Wali, H.; Ali, A.; Fateh, A. A.; Neogi, P. B.; Neogi, A.; Wang, Z. M. Gold nanoparticles-enabled efficient dual delivery of anticancer therapeutics to HeLa cells. Sci. Rep. 2018, 8, 2907.
Li, W.; Cao, Z. W.; Liu, R.; Liu, L. L.; Li, H.; Li, X.; Chen, Y. W.; Lu, C.; Liu, Y. Y. AuNPs as an important inorganic nanoparticle applied in drug carrier systems. Artif. Cells Nanomed. Biotechnol. 2019, 47, 4222–4233.
Cho, K.; Wang, X.; Nie, S. M.; Chen, Z.; Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 2008, 14, 1310–1316.
Amina, S. J.; Guo, B. A review on the synthesis and functionalization of gold nanoparticles as a drug delivery vehicle. Int. J. Nanomedicine 2020, 15, 9823–9857.
Jazayeri, M. H.; Amani, H.; Pourfatollah, A. A.; Pazoki-Toroudi, H.; Sedighimoghaddam, B. Various methods of gold nanoparticles (GNPs) conjugation to antibodies. Sens. Bio-Sens. Res. 2016, 9, 17–22.
Doane, T.; Burda, C. Nanoparticle mediated non-covalent drug delivery. Adv. Drug Deliv. Rev. 2013, 65, 607–621.
Sun, N.; Meng, X. Q.; Liu, Y. X.; Song, D.; Jiang, C. L.; Cai, J. Q. Applications of brain organoids in neurodevelopment and neurological diseases. J. Biomed. Sci. 2021, 28, 30.
Yakoub, A. M. Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain. Neural Regen Res 2019, 14, 757–761.
Eremeev, A. V.; Lebedeva, O. S.; Bogomiakova, M. E.; Lagarkova, M. A.; Bogomazova, A. N. Cerebral organoids-challenges to establish a brain prototype. Cells 2021, 10, 1790.
Bath, K. G.; Akins, M. R.; Lee, F. S. BDNF control of adult SVZ neurogenesis. Dev. Psychobiol. 2012, 54, 578–589.
Schäbitz, W. R.; Steigleder, T.; Cooper-Kuhn, C. M.; Schwab, S.; Sommer, C.; Schneider, A.; Kuhn, H. G. Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke 2007, 38, 2165–2172.
Sotnikov, D. V.; Berlina, A. N.; Ivanov, V. S.; Zherdev, A. V.; Dzantiev, B. B. Adsorption of proteins on gold nanoparticles: One or more layers? Colloids Surf. B Biointerfaces 2019, 173, 557–563.
Paşca, A. M.; Sloan, S. A.; Clarke, L. E.; Tian, Y.; Makinson, C. D.; Huber, N.; Kim, C. H.; Park, J. Y.; O’Rourke, N. A.; Nguyen, K. D. et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat. Methods 2015, 12, 671–678.
Arcila-Lozano, L. S.; Ríos-Corripio, M. A.; García-Pérez, B. E.; Jaramillo-Flores, M. E.; González, C. A.; Rocha-Gracia, R. C.; Gracia-Jiménez, J. M.; Rojas-López, M. Fluorescent bioconjugate based on gold nanoparticles for the determination of Staphylococcus aureus. Anal. Lett. 2017, 50, 1150–1167.
Hempstead, B. L. Brain-derived neurotrophic factor: Three ligands, many actions. Trans. Am. Clin. Climatol. Assoc. 2015, 126, 9–19.
Lee, E.; Jeon, H.; Lee, M.; Ryu, J.; Kang, C.; Kim, S.; Jung, J.; Kwon, Y. Molecular origin of AuNPs-induced cytotoxicity and mechanistic study. Sci. Rep. 2019, 9, 2494.
Lancaster, M. A.; Knoblich, J. A. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. 2014, 9, 2329–2340.
Huang, E. J.; Reichardt, L. F. Neurotrophins: Roles in neuronal development and function. Annu. Rev. Neurosci. 2001, 24, 677–736.
Ferreira, F. F.; Ribeiro, F. F.; Rodrigues, R. S.; Sebastião, A. M.; Xapelli, S. Brain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesis. Front. Cell Neurosci. 2018, 12, 441.
Qian, X. Y.; Jacob, F.; Song, M. M.; Nguyen, H. N.; Song, H. J.; Ming, G. L. Generation of human brain region-specific organoids using a miniaturized spinning bioreactor. Nat. Protoc. 2018, 13, 565–580.
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Acknowledgements
The authors greatly acknowledge the financial support from the Ministry of Science and ICT (No. 2021R1A2C2011195) and the Korea Research Institute of Chemical Technology of Republic of Korea (Nos. SI2131-50 and SI2152-20).
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