AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Article Link
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

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

Yang Zhou1,2,3Yifan Gao1,2,3Li Pang4Weirong Kang1,2,3Kwan Man4Weiping 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
Show Author Information

Graphical Abstract

Boron-dipyrromethene (BODIPY)-modified polyamidoamine (PAMAM) (BMP) can interact with proteins via ion–π, hydrophobic, and ionic interactions to form nanoparticles. Upon light irradiation, BODIPY groups conjugated on PAMAM can be cleaved, thereby inducing amine group exposure and nanoparticle dissociation to facilitate cytosolic protein delivery and endosome escape.

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.

Electronic Supplementary Material

Download File(s)
12274_2022_4948_MOESM1_ESM.pdf (1.4 MB)

References

[1]

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

[2]

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

[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.

[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.

[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.

[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.

[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.
[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.

[9]

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

[10]

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

[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.

[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.

[13]

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

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[26]

Salahpour Anarjan, F. Active targeting drug delivery nanocarriers: Ligands. Nano-Struct. Nano-Objects 2019, 19, 100370.

[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.

[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.

[29]

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

[30]

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

[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.

[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.

[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.

[34]

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

[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.

[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.

[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.

[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.
[39]

Singh, P. K.; Majumdar, P.; Singh, S. P. Advances in BODIPY photocleavable protecting groups. Coord. Chem. Rev. 2021, 449, 214193.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[56]

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

[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.

Nano Research
Pages 1042-1051
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
Topics:

990

Views

9

Crossref

7

Web of Science

8

Scopus

1

CSCD

Altmetrics

Received: 23 June 2022
Revised: 19 August 2022
Accepted: 23 August 2022
Published: 29 September 2022
© Tsinghua University Press 2022
Return