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Research Article | Online First

Lipocoacervate, a tunable vesicle for protein delivery

Chia-Wei Yeh1Nathaniel Wright1Chelsea Loh1Nabeen Chu2Yadong Wang1( )
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Kimball Hall 290, Ithaca 14853, USA
Human Biology, Health, and Society. College of Human Ecology, Cornell University, Ithaca 14853, USA
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Abstract

Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable. Here we report a self-assembling, tunable vesicle for the controlled delivery of growth factors and cytokines. Coacervate made of heparin and a biocompatible polycation, PEAD, forms the core of the vesicle; lipids form the membrane of the vesicle. We call this vesicle lipocoacervate (LipCo), which has a high affinity for growth factors and cytokines due to heparin. LipCo is a tunable protein delivery vehicle. The vesicle size is controlled through polymer and salt concentrations. Membrane functionalization enables potential for targeting capabilities with long-term storage through lyophilization. Importantly, the controlled delivery of therapeutics also avoids high toxicity to treated cells in vitro. Here we report on these key principles of LipCo assembly and design.

References

[1]

Nakashima KK, van Haren MHI, André AAM, Robu I, Spruijt E. Active coacervate droplets are protocells that grow and resist Ostwald ripening. Nat Commun. 2021, 12, 3819.

[2]

Neitzel, A. E.; Fang, Y. N.; Yu, B. Y.; Rumyantsev, A. M.; De Pablo, J. J.; Tirrell, M. V. Polyelectrolyte complex coacervation across a broad range of charge densities. Macromolecules 2021, 54, 6878–6890.

[3]

Kembaren, R.; Kleijn, J. M.; Borst, J. W.; Kamperman, M.; Hofman, A. H. Enhanced stability of complex coacervate core micelles following different core-crosslinking strategies. Soft Matter 2022, 18, 3052–3062.

[4]

Horn, J. M.; Kapelner, R. A.; Obermeyer, A. C. Macro- and microphase separated protein-polyelectrolyte complexes: Design parameters and current progress. Polymers 2019, 11, 578.

[5]

Awada, H. K.; Long, D. W.; Wang, Z.; Hwang, M. P.; Kim, K.; Wang, Y. A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction. Biomaterials 2017, 125, 65–80.

[6]

Chu, H.; Chen, C. W.; Huard, J.; Wang, Y. D. The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium. Biomaterials 2013, 34, 1747–1756.

[7]

Li, R.; Zou, S.; Wu, Y. Q.; Li, Y. Y.; Khor, S.; Mao, Y. Q.; He, H. C.; Xu, K.; Zhang, H. Y.; Li, X. K. et al. Heparin-based coacervate of bFGF facilitates peripheral nerve regeneration by inhibiting endoplasmic reticulum stress following sciatic nerve injury. Oncotarget 2017, 8, 48086–48097.

[8]

Wu, Y. Q.; Wang, Z. G.; Cai, P. T.; Jiang, T.; Li, Y. Y.; Yuan, Y.; Li, R.; Khor, S.; Lu, Y. F.; Wang, J. et al. Dual delivery of bFGF- and NGF-binding coacervate confers neuroprotection by promoting neuronal proliferation. Cell. Physiol. Biochem. 2018, 47, 948–956.

[9]

Lee, K.; Silva, E. A.; Mooney, D. J. Growth factor delivery-based tissue engineering: General approaches and a review of recent developments. J. Roy. Soc. Interface 2011, 8, 153–170.

[10]

Capila, I.; Linhardt, R. J. Heparin-protein interactions. 3.0.CO;2-B">Angew. Chem., Int. Ed. 2002, 41, 390–412.

[11]

Wang, H. Y.; Moon, C.; Shin, M. C.; Wang, Y. P.; He, H. N.; Yang, V. C.; Huang, Y. Z. Heparin-regulated prodrug-type macromolecular theranostic systems for cancer therapy. Nanotheranostics 2017, 1, 114–130.

[12]

Hwang, M. P.; Fecek, R. J.; Qin, T. Y.; Storkus, W. J.; Wang, Y. D. Single injection of IL-12 coacervate as an effective therapy against B16-F10 melanoma in mice. J. Control. Release 2020, 318, 270–278.

[13]

Gao, X. Q.; Hwang, M. P.; Wright, N.; Lu, A. P.; Ruzbarsky, J. J.; Huard, M.; Cheng, H. Z.; Mullen, M.; Ravuri, S.; Wang, B. et al. The use of heparin/polycation coacervate sustain release system to compare the bone regenerative potentials of 5 BMPs using a critical sized calvarial bone defect model. Biomaterials 2022, 288, 121708.

[14]

Chen, W. C. W.; Lee, B. G.; Park, D. W.; Kim, K.; Chu, H.; Kim, K.; Huard, J.; Wang, Y. D. Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair. Biomaterials 2015, 72, 138–151.

[15]

Yeh, C. W.; Wang, Y. D. Coacervate-filled lipid vesicles for protein delivery. Macromol. Biosci. 2023, 23, 2200538.

[16]

Ban, E.; Kim, A. Coacervates: Recent developments as nanostructure delivery platforms for therapeutic biomolecules. Int. J. Pharm. 2022, 624, 122058.

[17]

Kitamura, T.; Tange, T.; Terasawa, T.; Chiba, S.; Kuwaki, T.; Miyagawa, K.; Piao, Y. F.; Miyazono, K.; Urabe, A.; Takaku, F. Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J. Cell. Physiol. 1989, 140, 323–334.

[18]

Thomson, C. A.; Olson, M.; Jackson, L. M.; Schrader, J. W. A simplified method for the efficient refolding and purification of recombinant human GM-CSF. PLoS One 2012, 7, e49891.

[19]

Ding, X. C.; Miller, P. G.; Hwang, M. P.; Fu, J. Y.; Wang, Y. D. Scale-up synthesis of a polymer designed for protein therapy. Eur. Polym. J. 2019, 117, 353–362.

[20]

Takayama, Y.; Kusamori, K.; Nishikawa, M. Click chemistry as a tool for cell engineering and drug delivery. Molecules 2019, 24, 172.

[21]

McTigue, W. C. B.; Perry, S. L. Design rules for encapsulating proteins into complex coacervates. Soft Matter 2019, 15, 3089–3103.

[22]

Baskin, J. M.; Prescher, J. A.; Laughlin, S. T.; Agard, N. J.; Chang, P. V.; Miller, I. A.; Lo, A.; Codelli, J. A.; Bertozzi, C. R. Copper-free click chemistry for dynamic in vivo imaging. Proc. Natl. Acad. Sci. USA 2007, 104, 16793–16797.

[23]

Devaraj, N. K.; Finn, M. G. Introduction: Click chemistry. Chem. Rev. 2021, 121, 6697–6698.

[24]

Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation. Angew. Chem., Int. Ed. 2009, 48, 9879–9883.

[25]

Liu, P.; Chen, G. L.; Zhang, J. C. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules 2022, 27, 1372.

[26]

Franzé, S.; Selmin, F.; Samaritani, E.; Minghetti, P.; Cilurzo, F. Lyophilization of liposomal formulations: Still necessary, still challenging. Pharmaceutics 2018, 10, 139.

[27]

Yu, J. Y.; Chuesiang, P.; Shin, G. H.; Park, H. J. Post-processing techniques for the improvement of liposome stability. Pharmaceutics 2021, 13, 1023.

[28]

Becher, B.; Tugues, S.; Greter, M. GM-CSF: From growth factor to central mediator of tissue inflammation. Immunity 2016, 45, 963–973.

[29]

Kumar, A.; Taghi Khani, A.; Sanchez Ortiz, A.; Swaminathan, S. GM-CSF: A double-edged sword in cancer immunotherapy. Front. Immunol. 2022, 13, 901277.

[30]

Lang, F. M.; Lee, K. M. C.; Teijaro, J. R.; Becher, B.; Hamilton, J. A. GM-CSF-based treatments in COVID-19: Reconciling opposing therapeutic approaches. Nat. Rev. Immunol. 2020, 20, 507–514.

[31]

Chuang, Y. M.; He, L. M.; Pinn, M. L.; Tsai, Y. C.; Cheng, M. A.; Farmer, E.; Karakousis, P. C.; Hung, C. F. Albumin fusion with granulocyte-macrophage colony-stimulating factor acts as an immunotherapy against chronic tuberculosis. Cell. Mol. Immunol. 2021, 18, 2393–2401.

[32]

Papież, M. A.; Krzyściak, W. Biological therapies in the treatment of cancer-update and new directions. Int. J. Mol. Sci. 2021, 22, 11694.

[33]

Link-Gelles, R.; Levy, M. E.; Natarajan, K.; Reese, S. E.; Naleway, A. L.; Grannis, S. J.; Klein, N. P.; Desilva, M. B.; Ong, T. C.; Gaglani, M. et al. Estimation of COVID-19 mRNA vaccine effectiveness and COVID-19 illness and severity by vaccination status during omicron BA.4 and BA.5 sublineage periods. JAMA Netw. Open 2023, 6, e232598.

[34]
Puranik, A.; Lenehan, P. J.; Silvert, E.; Niesen, M. J. M.; Corchado-Garcia, J.; O'Horo, J. C.; Virk, A.; Swift, M. D.; Halamka, J.; Badley, A. D. et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of alpha and delta variant prevalence. medrxiv, 2021, DOI: 10.1101/2021.08.06. 21261707. https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v3 (accessed Mar 3, 2024).
[35]

Alshawwa, S. Z.; Kassem, A. A.; Farid, R. M.; Mostafa, S. K.; Labib, G. S. Nanocarrier drug delivery systems: Characterization, limitations, future perspectives and implementation of artificial intelligence. Pharmaceutics 2022, 14, 883.

[36]

Mitchell, M. J.; Billingsley, M. M.; Haley, R. M.; Wechsler, M. E.; Peppas, N. A.; Langer, R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021, 20, 101–124.

[37]

Caldorera-Moore, M.; Vela Ramirez, J. E.; Peppas, N. A. Transport and delivery of interferon-α through epithelial tight junctions via pH-responsive poly(methacrylic acid-grafted-ethylene glycol) nanoparticles. J. Drug Target. 2019, 27, 582–589.

[38]

Huang, K. W.; Hsu, F. F.; Qiu, J. T.; Chern, G. J.; Lee, Y. A.; Chang, C. C.; Huang, Y. T.; Sung, Y. C.; Chiang, C. C.; Huang, R. L. et al. Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer. Sci. Adv. 2020, 6, eaax5032.

[39]

Lu, T. M.; Liese, S.; Schoenmakers, L.; Weber, C. A.; Suzuki, H.; Huck, W. T. S.; Spruijt, E. Endocytosis of coacervates into liposomes. J. Am. Chem. Soc. 2022, 144, 13451–13455.

[40]

Duan, H. X.; Liu, C.; Hou, Y.; Liu, Y. H.; Zhang, Z. A.; Zhao, H. M.; Xin, X.; Liu, W.; Zhang, X. T.; Chen, L. Q. et al. Sequential delivery of quercetin and paclitaxel for the fibrotic tumor microenvironment remodeling and chemotherapy potentiation via a dual-targeting hybrid micelle-in-liposome system. ACS Appl. Mater. Interfaces 2022, 14, 10102–10116.

[41]

Cheng, X. W.; Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 2016, 99, 129–137.

[42]

Hersh, A. M.; Alomari, S.; Tyler, B. M. Crossing the blood-brain barrier: Advances in nanoparticle technology for drug delivery in neuro-oncology. Int. J. Mol. Sci. 2022, 23, 4153.

[43]

Fu, Z. W.; Li, S. J.; Han, S. F.; Shi, C.; Zhang, Y. Antibody drug conjugate: The “biological missile” for targeted cancer therapy. Signal Transduct. Target Ther. 2022, 7, 93.

[44]

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

Nano Research
Cite this article:
Yeh C-W, Wright N, Loh C, et al. Lipocoacervate, a tunable vesicle for protein delivery. Nano Research, 2024, https://doi.org/10.1007/s12274-024-6889-6
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Received: 03 March 2024
Revised: 15 July 2024
Accepted: 15 July 2024
Published: 10 August 2024
© Tsinghua University Press 2024
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