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Nano Research 2023, 16(1): 1042-1051 https://doi.org/10.1007/s12274-022-4948-4
Research Article | Issue | Published: 29 September 2022

A green light-enhanced cytosolic protein delivery platform based on BODIPY-protein interactions

Show Author's Information Yang Zhou1,2,3,  Yifan Gao1,2,3,  Li Pang4,  Weirong Kang1,2,3,  Kwan Man4,  Weiping Wang1,2,3( )
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China
Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Keywords:
photoresponsive nanoparticles, protein delivery, intracellular delivery, polyamidoamine (PAMAM), boron-dipyrromethene (BODIPY)
Topics:
Nano biology
Cite this article:
Zhou Y, Gao Y, Pang L, et al. A green light-enhanced cytosolic protein delivery platform based on BODIPY-protein interactions. Nano Research, 2023, 16(1): 1042-1051. https://doi.org/10.1007/s12274-022-4948-4
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Abstract Full text Electronic supplementary material About this article

Development of cytosolic protein delivery platforms brings new possibilities for various incurable diseases. Strategies based on polymer/protein self-assembly have shown their potential in protein delivery. However, versatile photocontrolled platforms based on self-assembly for protein delivery are seldom reported. Herein, we report a boron-dipyrromethene (BODIPY)-modified polyamidoamine (PAMAM) with excellent photo-controllability and efficiency for the cytosolic delivery of various proteins. High serum stability was achieved by coating hyaluronic acid and human serum albumin on the surface of BODIPY-modified PAMAM/protein nanoparticles. The nanoparticles under green light irradiation allowed efficient intracellular delivery of multiple cargo proteins with different charges and molecular weights and promoted endosome escape. The study provides valuable guidance for the development of BODIPY derivative-based protein delivery systems and advances the research in intracellular protein delivery.


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Electronic supplementary material
About this article

A green light-enhanced cytosolic protein delivery platform based on BODIPY-protein interactions

Show Author's information Yang Zhou1,2,3, Yifan Gao1,2,3, Li Pang4, Weirong Kang1,2,3, Kwan Man4, Weiping Wang1,2,3( )
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China
Department of Surgery, School of Clinical Medicine, HKU-SZH & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Abstract

Development of cytosolic protein delivery platforms brings new possibilities for various incurable diseases. Strategies based on polymer/protein self-assembly have shown their potential in protein delivery. However, versatile photocontrolled platforms based on self-assembly for protein delivery are seldom reported. Herein, we report a boron-dipyrromethene (BODIPY)-modified polyamidoamine (PAMAM) with excellent photo-controllability and efficiency for the cytosolic delivery of various proteins. High serum stability was achieved by coating hyaluronic acid and human serum albumin on the surface of BODIPY-modified PAMAM/protein nanoparticles. The nanoparticles under green light irradiation allowed efficient intracellular delivery of multiple cargo proteins with different charges and molecular weights and promoted endosome escape. The study provides valuable guidance for the development of BODIPY derivative-based protein delivery systems and advances the research in intracellular protein delivery.

Keywords: photoresponsive nanoparticles, protein delivery, intracellular delivery, polyamidoamine (PAMAM), boron-dipyrromethene (BODIPY)

References(57)

[1]

Leader, B.; Baca, Q. J.; Golan, D. E. Protein therapeutics: A summary and pharmacological classification. Nat. Rev. Drug Discov. 2008, 7, 21–39.
DOI Google Scholar
[2]

Antosova, Z.; Mackova, M.; Kral, V.; Macek, T. Therapeutic application of peptides and proteins: Parenteral forever? Trends Biotechnol. 2009, 27, 628–635.
DOI Google Scholar
[3]

Tong, T.; Wang, L. Y.; You, X. R.; Wu, J. Nano and microscale delivery platforms for enhanced oral peptide/protein bioavailability. Biomater. Sci. 2020, 8, 5804–5823.
DOI Google Scholar
[4]

Kintzing, J. R.; Filsinger Interrante, M. V.; Cochran, J. R. Emerging strategies for developing next-generation protein therapeutics for cancer treatment. Trends Pharmacol. Sci. 2016, 37, 993–1008.
DOI Google Scholar
[5]

Serna, N.; Sánchez-García, L.; Unzueta, U.; Díaz, R.; Vázquez, E.; Mangues, R.; Villaverde, A. Protein-based therapeutic killing for cancer therapies. Trends Biotechnol. 2018, 36, 318–335.
DOI Google Scholar
[6]

Sharma, G.; Sharma, A. R.; Bhattacharya, M.; Lee, S. S.; Chakraborty, C. CRISPR-Cas9: A preclinical and clinical perspective for the treatment of human diseases. Mol. Ther. 2021, 29, 571–586.
DOI Google Scholar
[7]
Golchin, A.; Shams, F.; Karami, F. Advancing mesenchymal stem cell therapy with CRISPR/Cas9 for clinical trial studies. In Cell Biology and Translational Medicine, Volume 8: Stem Cells in Regenerative Medicine; Turksen, K., Ed.; Springer: Cham, 2020; pp 89–100.
DOI
[8]

Suzuki, H.; Tango, T. A multicenter, randomized, controlled clinical trial of interferon alfacon-1 in comparison with lymphoblastoid interferon-alpha in patients with high-titer chronic hepatitis C virus infection. Hepatol. Res. 2002, 22, 1–12.
DOI Google Scholar
[9]

Krejsa, C.; Rogge, M.; Sadee, W. Protein therapeutics: New applications for pharmacogenetics. Nat. Rev. Drug Discov. 2006, 5, 507–521.
DOI Google Scholar
[10]

Pavlou, A. K.; Reichert, J. M. Recombinant protein therapeutics-success rates, market trends and values to 2010. Nat. Biotechnol. 2004, 22, 1513–1519.
DOI Google Scholar
[11]

Wu, D.; Qin, M.; Xu, D.; Wang, L.; Liu, C. Y.; Ren, J.; Zhou, G.; Chen, C.; Yang, F. M.; Li, Y. Y. et al. A bioinspired platform for effective delivery of protein therapeutics to the central nervous system. Adv. Mater. 2019, 31, 1807557.
DOI Google Scholar
[12]

Le Saux, S.; Aubert-Pouëssel, A.; Ouchait, L.; Mohamed, K. E.; Martineau, P.; Guglielmi, L.; Devoisselle, J. M.; Legrand, P.; Chopineau, J.; Morille, M. Nanotechnologies for intracellular protein delivery: Recent progress in inorganic and organic nanocarriers. Adv. Ther. 2021, 4, 2100009.
DOI Google Scholar
[13]

Vaishya, R.; Khurana, V.; Patel, S.; Mitra, A. K. Long-term delivery of protein therapeutics. Expert Opin. Drug Deliv. 2015, 12, 415–440.
DOI Google Scholar
[14]

Fang, Y. Z.; Vadlamudi, M.; Huang, Y. B.; Guo, X. Lipid-coated, pH-sensitive magnesium phosphate particles for intracellular protein delivery. Pharm. Res. 2019, 36, 81.
DOI Google Scholar
[15]

Aksoy, Y. A.; Yang, B. Y.; Chen, W. J.; Hung, T.; Kuchel, R. P.; Zammit, N. W.; Grey, S. T.; Goldys, E. M.; Deng, W. Spatial and temporal control of CRISPR-Cas9-mediated gene editing delivered via a light-triggered liposome system. ACS Appl. Mater. Interfaces 2020, 12, 52433–52444.
DOI Google Scholar
[16]

Meka, A. K.; Abbaraju, P. L.; Song, H.; Xu, C.; Zhang, J.; Zhang, H. W.; Yu, M. H.; Yu, C. Z. A vesicle supra-assembly approach to synthesize amine-functionalized hollow dendritic mesoporous silica nanospheres for protein delivery. Small 2016, 12, 5169–5177.
DOI Google Scholar
[17]

Tang, R.; Jiang, Z. W.; Ray, M.; Hou, S.; Rotello, V. M. Cytosolic delivery of large proteins using nanoparticle-stabilized nanocapsules. Nanoscale 2016, 8, 18038–18041.
DOI Google Scholar
[18]

Liu, C. Y.; Wan, T.; Wang, H.; Zhang, S.; Ping, Y.; Cheng, Y. Y. A boronic acid-rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing. Sci. Adv. 2019, 5, eaaw8922.
DOI Google Scholar
[19]

Zhao, H.; Lin, Z. Y.; Yildirimer, L.; Dhinakar, A.; Zhao, X.; Wu, J. Polymer-based nanoparticles for protein delivery: Design, strategies and applications. J. Mater. Chem. B 2016, 4, 4060–4071.
DOI Google Scholar
[20]

Wu, J.; Kamaly, N.; Shi, J. J.; Zhao, L. L.; Xiao, Z. Y.; Hollett, G.; John, R.; Ray, S.; Xu, X. Y.; Zhang, X. Q. et al. Development of multinuclear polymeric nanoparticles as robust protein nanocarriers. Angew. Chem., Int. Ed. 2014, 53, 8975–8979.
DOI Google Scholar
[21]

Zhang, N.; Yan, Z. Q.; Zhao, X.; Chen, Q.; Ma, M. M. Efficient mini-transporter for cytosolic protein delivery. ACS Appl. Mater. Interfaces 2016, 8, 25725–25732.
DOI Google Scholar
[22]

Zhang, S.; Lv, J.; Gao, P.; Feng, Q. Y.; Wang, H.; Cheng, Y. Y. A pH-responsive phase-transition polymer with high serum stability in cytosolic protein delivery. Nano Lett. 2021, 21, 7855–7861.
DOI Google Scholar
[23]

Fu, L. Y.; Hua, X. W.; Jiang, X. Y.; Shi, J. J. Multistage systemic and cytosolic protein delivery for effective cancer treatment. Nano Lett. 2022, 22, 111–118.
DOI Google Scholar
[24]

Backlund, C. M.; Hango, C. R.; Minter, L. M.; Tew, G. N. Protein and antibody delivery into difficult-to-transfect cells by polymeric peptide mimics. ACS Appl. Bio Mater. 2020, 3, 180–185.
DOI Google Scholar
[25]

Murugan, B.; Sagadevan, S.; Fatimah, I.; Oh, W. C.; Motalib Hossain, M. A.; Johan, M. R. Smart stimuli-responsive nanocarriers for the cancer therapy-nanomedicine. Nanotechnol. Rev. 2021, 10, 933–953.
DOI Google Scholar
[26]

Salahpour Anarjan, F. Active targeting drug delivery nanocarriers: Ligands. Nano-Struct. Nano-Objects 2019, 19, 100370.
DOI Google Scholar
[27]

Lv, J.; Wang, C. P.; Li, H. R.; Li, Z.; Fan, Q. Q.; Zhang, Y.; Li, Y. W.; Wang, H.; Cheng, Y. Y. Bifunctional and bioreducible dendrimer bearing a fluoroalkyl tail for efficient protein delivery both in vitro and in vivo. Nano Lett. 2020, 20, 8600–8607.
DOI Google Scholar
[28]

Qiao, Y. T.; Wan, J. Q.; Zhou, L. Q.; Ma, W.; Yang, Y. Y.; Luo, W. X.; Yu, Z. Q.; Wang, H. X. Stimuli-responsive nanotherapeutics for precision drug delivery and cancer therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2019, 11, e1527.
DOI Google Scholar
[29]

Rwei, A. Y.; Wang, W. P.; Kohane, D. S. Photoresponsive nanoparticles for drug delivery. Nano Today 2015, 10, 451–467.
DOI Google Scholar
[30]

Li, Y. F.; Zhang, Y. M.; Wang, W. P. Phototriggered targeting of nanocarriers for drug delivery. Nano Res. 2018, 11, 5424–5438.
DOI Google Scholar
[31]

Hentzen, N. B.; Mogaki, R.; Otake, S.; Okuro, K.; Aida, T. Intracellular photoactivation of caspase-3 by molecular glues for spatiotemporal apoptosis induction. J. Am. Chem. Soc. 2020, 142, 8080–8084.
DOI Google Scholar
[32]

Pan, Y. C.; Yang, J. J.; Luan, X. W.; Liu, X. L.; Li, X. Q.; Yang, J.; Huang, T.; Sun, L.; Wang, Y. Z.; Lin, Y. H. et al. Near-infrared upconversion-activated CRISPR-Cas9 system: A remote-controlled gene editing platform. Sci. Adv. 2019, 5, eaav7199.
DOI Google Scholar
[33]

He, H.; Chen, Y. B.; Li, Y. J.; Song, Z. Y.; Zhong, Y. N.; Zhu, R. Y.; Cheng, J. J.; Yin, L. C. Effective and selective anti-cancer protein delivery via all-functions-in-one nanocarriers coupled with visible light-responsive, reversible protein engineering. Adv. Funct. Mater. 2018, 28, 1706710.
DOI Google Scholar
[34]

Gu, Z.; Biswas, A.; Zhao, M. X.; Tang, Y. Tailoring nanocarriers for intracellular protein delivery. Chem. Soc. Rev. 2011, 40, 3638–3655.
DOI Google Scholar
[35]

Li, Y. F.; Zhou, Y.; Wang, T. Y.; Long, K. Q.; Zhang, Y. M.; Wang, W. P. Photoenhanced cytosolic protein delivery based on a photocleavable group-modified dendrimer. Nanoscale 2021, 13, 17784–17792.
DOI Google Scholar
[36]

Slanina, T.; Shrestha, P.; Palao, E.; Kand, D.; Peterson, J. A.; Dutton, A. S.; Rubinstein, N.; Weinstain, R.; Winter, A. H.; Klán, P. In search of the perfect photocage: Structure-reactivity relationships in meso-methyl BODIPY photoremovable protecting groups. J. Am. Chem. Soc. 2017, 139, 15168–15175.
DOI Google Scholar
[37]

Lv, W.; Li, Y. F.; Li, F. Y.; Lan, X.; Zhang, Y. M.; Du, L. L.; Zhao, Q.; Phillips, D. L.; Wang, W. P. Upconversion-like photolysis of BODIPY-based prodrugs via a one-photon process. J. Am. Chem. Soc. 2019, 141, 17482–17486.
DOI Google Scholar
[38]
Long, K. Q.; Wang, Y. F.; Lv, W.; Yang, Y.; Xu, S. T.; Zhan, C. Y.; Wang, W. P. Photoresponsive prodrug-dye nanoassembly for in-situ monitorable cancer therapy. Bioeng. Transl. Med., in press, https://doi.org/10.1002/btm2.10311.
DOI
[39]

Singh, P. K.; Majumdar, P.; Singh, S. P. Advances in BODIPY photocleavable protecting groups. Coord. Chem. Rev. 2021, 449, 214193.
DOI Google Scholar
[40]

Marfin, Y. S.; Aleksakhina, E. L.; Merkushev, D. A.; Rumyantsev, E. V.; Tomilova, I. K. Interaction of BODIPY dyes with the blood plasma proteins. J. Fluoresc. 2016, 26, 255–261.
DOI Google Scholar
[41]

Ksenofontov, A. A.; Bocharov, P. S.; Antina, E. V. Interaction of tetramethyl-substituted BODIPY dye with bovine serum albumin: Spectroscopic study and molecular docking. J. Photochem. Photobiol. A:Chem. 2019, 368, 254–257.
DOI Google Scholar
[42]

Ribić, V. R.; Stojanović, S. Đ.; Zlatović, M. V. Anion–π interactions in active centers of superoxide dismutases. Int. J. Biol. Macromol. 2018, 106, 559–568.
DOI Google Scholar
[43]

Mahadevi, A. S.; Sastry, G. N. Cation–π interaction: Its role and relevance in chemistry, biology, and material science. Chem. Rev. 2013, 113, 2100–2138.
DOI Google Scholar
[44]

Xu, W.; Luo, F. Q.; Tong, Q. S.; Li, J. X.; Miao, W. M.; Zhang, Y.; Xu, C. F.; Du, J. Z.; Wang, J. An intracellular pH-actuated polymer for robust cytosolic protein delivery. CCS Chem. 2021, 3, 431–442.
DOI Google Scholar
[45]

Lv, J.; He, B. W.; Yu, J. W.; Wang, Y. T.; Wang, C. P.; Zhang, S.; Wang, H.; Hu, J. J.; Zhang, Q.; Cheng, Y. Y. Fluoropolymers for intracellular and in vivo protein delivery. Biomaterials 2018, 182, 167–175.
DOI Google Scholar
[46]

Xu, J.; Lv, J.; Zhuang, Q.; Yang, Z. J.; Cao, Z. Q.; Xu, L. G.; Pei, P.; Wang, C. Y.; Wu, H. F.; Dong, Z. L. et al. A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy. Nat. Nanotechnol. 2020, 15, 1043–1052.
DOI Google Scholar
[47]

Palanikumar, L.; Kim, J.; Oh, J. Y.; Choi, H.; Park, M. H.; Kim, C.; Ryu, J. H. Hyaluronic acid-modified polymeric gatekeepers on biodegradable mesoporous silica nanoparticles for targeted cancer therapy. ACS Biomater. Sci. Eng. 2018, 4, 1716–1722.
DOI Google Scholar
[48]

Iversen, T. G.; Skotland, T.; Sandvig, K. Endocytosis and intracellular transport of nanoparticles: Present knowledge and need for future studies. Nano Today 2011, 6, 176–185.
DOI Google Scholar
[49]

Rennick, J. J.; Johnston, A. P. R.; Parton, R. G. Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics. Nat. Nanotechnol. 2021, 16, 266–276.
DOI Google Scholar
[50]

Luo, H. C.; Li, N.; Yan, L.; Mai, K. J.; Sun, K.; Wang, W.; Lao, G. J.; Yang, C.; Zhang, L. M.; Ren, M. Comparison of the cellular transport mechanism of cationic, star-shaped polymers and liposomes in HaCat cells. Int. J. Nanomed. 2017, 12, 1085–1096.
DOI Google Scholar
[51]

Lönn, P.; Kacsinta, A. D.; Cui, X. S.; Hamil, A. S.; Kaulich, M.; Gogoi, K.; Dowdy, S. F. Enhancing endosomal escape for intracellular delivery of macromolecular biologic therapeutics. Sci. Rep. 2016, 6, 32301.
DOI Google Scholar
[52]

Freeman, E. C.; Weiland, L. M.; Meng, W. S. Modeling the proton sponge hypothesis: Examining proton sponge effectiveness for enhancing intracellular gene delivery through multiscale modeling. J. Biomater. Sci. Polym. Ed. 2013, 24, 398–416.
DOI Google Scholar
[53]

Dong, S. X. M.; Caballero, R.; Ali, H.; Roy, D. L. F.; Cassol, E.; Kumar, A. Transfection of hard-to-transfect primary human macrophages with Bax siRNA to reverse Resveratrol-induced apoptosis. RNA Biol. 2020, 17, 755–764.
DOI Google Scholar
[54]

Olazabal, I. M.; Martín-Cofreces, N. B.; Mittelbrunn, M.; del Hoyo, G. M.; Alarcón, B.; Sánchez-Madrid, F. Activation outcomes induced in naive CD8 T-cells by macrophages primed via “phagocytic” and nonphagocytic pathways. Mol. Biol. Cell 2008, 19, 701–710.
DOI Google Scholar
[55]

Xu, J.; Wang, H.; Xu, L. G.; Chao, Y.; Wang, C. Y.; Han, X.; Dong, Z. L.; Chang, H.; Peng, R.; Cheng, Y. Y. et al. Nanovaccine based on a protein-delivering dendrimer for effective antigen cross-presentation and cancer immunotherapy. Biomaterials 2019, 207, 1–9.
DOI Google Scholar
[56]

Sitkowska, K.; Feringa, B. L.; Szymański, W. Green-light-sensitive BODIPY photoprotecting groups for amines. J. Org. Chem. 2018, 83, 1819–1827.
DOI Google Scholar
[57]

Veelken, C.; Bakker, G. J.; Drell, D.; Friedl, P. Single cell-based automated quantification of therapy responses of invasive cancer spheroids in organotypic 3D culture. Methods 2017, 128, 139–149.
DOI Google Scholar
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Publication history
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Acknowledgements

Publication history

Received: 23 June 2022
Revised: 19 August 2022
Accepted: 23 August 2022
Published: 29 September 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the Research Grants Council of Hong Kong (Early Career Scheme, No. 27115220) and Ming Wai Lau Centre for Reparative Medicine Associate Member Program. The authors acknowledge the assistance of The University of Hong Kong Li Ka Shing Faculty of Medicine Faculty Core Facility.

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