Polypeptide-based amphiphilic brush copolymers as unimolecular micelles: synthesis, characterisation, and encapsulation study

Yukui Zheng; Miao Pan; Chao Lu; Daojun Liu

Polypeptide-based amphiphilic brush copolymers as unimolecular micelles: synthesis, characterisation, and encapsulation study

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Author(s): Yukui Zheng¹ ; Miao Pan¹ ; Chao Lu¹ ; Daojun Liu¹
- Affiliations: 1: Medical College, Shantou University , Shantou 515041 , People's Republic of China
Source: Volume 13, Issue 9, September 2018, p. 1329 – 1334
DOI: 10.1049/mnl.2018.5094 , Online ISSN 1750-0443

Received 13/03/2018, Accepted 18/05/2018, Revised 26/04/2018, Published 01/09/2018

Polypeptide-based amphiphilic brush copolymers PLL-g-(PBLG-b-PEG) and PLL-g-(PZLL-b-PEG) with a poly(L-lysine) (PLL) backbone and amphiphilic oligo(γ-benzyl-L-glutamate)-b-poly(ethylene glycol) (PBLG-b-PEG) or oligo(ε-benzyloxycarbonyl-L-lysine)-b-poly(ethylene glycol) (PZLL-b-PEG) side chains were synthesised, characterised, and evaluated as unimolecular nanocontainers to encapsulate hydrophobic guest molecules. The structure of these brush polymers was modulated by tuning the length of the PLL, PBLG/PZLL, and PEG segments. The final products were characterised with ¹H nuclear magnetic resonance and gel permeation chromatography. The morphology and aggregation behaviours of brush copolymers were examined by using a transmission electron microscope and dynamic light scattering. It was revealed that these water-soluble brush copolymers resembled unimolecular micelles in an aqueous solution. An encapsulation study was performed using pyrene and oil red O as the model compounds, and the results showed that hydrophobic molecules could be solubilised in these unimolecular micelles with high loading capacities. The synthesised polypeptide-based amphiphilic brush copolymers could serve as promising unimolecular nanocarriers for the delivery of hydrophobic drugs.

References

1. 1)
  - 5. Talelli, M., Iman, M., Varkouhi, A.-K., et al: ‘Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin’, Biomaterials, 2010, 31, (30), pp. 7797–7804 (doi: 10.1016/j.biomaterials.2010.07.005).
2. 2)
  - 13. Johnson, J.-A., Lu, Y.-Y., Burts, A.-O., et al: ‘Drug-loaded, bivalent-bottle-brush polymers by graft-through ROMP’, Macromolecules, 2010, 43, (24), pp. 10326–10335 (doi: 10.1021/ma1021506).
3. 3)
  - 28. Lu, H., Cheng, J.: ‘Hexamethyldisilazane-mediated controlled polymerization of α-amino acid N-carboxyanhydrides’, J. Am. Chem. Soc., 2007, 129, (46), pp. 14114–14115 (doi: 10.1021/ja074961q).
4. 4)
  - 12. Zeng, X., Li, J., Zheng, J., et al: ‘Amphiphilic cylindrical copolypeptide brushes as potential nanocarriers for the simultaneous encapsulation of hydrophobic and cationic drugs’, Colloid Surf. B, 2012, 94, (7), pp. 324–332 (doi: 10.1016/j.colsurfb.2012.02.012).
5. 5)
  - 19. Bae, Y., Kataoka, K.: ‘Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers’, Adv. Drug Deliv. Rev., 2009, 61, (10), pp. 768–784 (doi: 10.1016/j.addr.2009.04.016).
6. 6)
  - 15. Yu, Y., Chen, C.-K., Law, W.-C., et al: ‘Degradable brush polymer-drug conjugate for pH-responsive release of doxorubicin’, Polym. Chem., 2015, 6, (6), pp. 953–961 (doi: 10.1039/C4PY01194E).
7. 7)
  - 22. Zhuang, W., Liao, L., Chen, H., et al: ‘Water soluble star-block copolypeptides: towards biodegradable nanocarriers for versatile and simultaneous encapsulation’, Macromol. Rapid Commun., 2009, 30, (11), pp. 920–924 (doi: 10.1002/marc.200800807).
8. 8)
  - 23. Yan, Y., Wei, D., Li, J., et al: ‘A poly(L-lysine)-based hydrophilic star block co-polymer as a protein nanocarrier with facile encapsulation and pH-responsive release’, Acta Biomater., 2012, 8, (6), pp. 2113–2120 (doi: 10.1016/j.actbio.2012.02.016).
9. 9)
  - 14. Yu, Y., Chen, C.-K., Law, W.-C., et al: ‘Well-defined degradable brush polymer-drug conjugates for sustained delivery of paclitaxel’, Mol. Pharm., 2013, 10, (3), pp. 867–874 (doi: 10.1021/mp3004868).
10. 10)
  - 26. Kricheldorf, H.-R.: ‘Polypeptides and 100 years of chemistry of α–amino acid N-carboxyanhydrides’, Angew. Chem. Int. Ed., 2006, 45, (35), pp. 5752–5784 (doi: 10.1002/anie.200600693).
11. 11)
  - 20. Sun, H., Meng, F., Dias, A.-A., et al: ‘α-Amino acid containing degradable polymers as functional biomaterials: rational design, synthetic pathway, and biomedical applications’, Biomacromolecules, 2011, 12, (6), pp. 1937–1955 (doi: 10.1021/bm200043u).
12. 12)
  - 17. Li, X., Qian, Y., Liu, T., et al: ‘Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging’, Biomaterials, 2011, 32, (27), pp. 6595–6605 (doi: 10.1016/j.biomaterials.2011.05.049).
13. 13)
  - 24. Li, J., Li, J., Xu, S., et al: ‘Hydrophobic oligopeptide-based star-block copolymers as unimolecular nanocarriers for poorly water-soluble drugs’, Colloid Surf. B, 2013, 110, (110C), pp. 183–190 (doi: 10.1016/j.colsurfb.2013.04.049).
14. 14)
  - 11. Sun, Y., Yan, X., Yuan, T., et al: ‘Disassemblable micelles based on reduction-degradable amphiphilic graft copolymers for intracellular delivery of doxorubicin’, Biomaterials, 2010, 31, (27), pp. 7124–7131 (doi: 10.1016/j.biomaterials.2010.06.011).
15. 15)
  - 6. Yuan, C., Xu, Y., Liao, Y., et al: ‘Morphology tailoring and temperature sensitivity control of waist cross-linked micelles and evaluation of their application as intelligent drug carriers’, J. Mater. Chem., 2010, 20, (44), pp. 9968–9975 (doi: 10.1039/c0jm02023k).
16. 16)
  - 3. Li, Z.-L., Huang, Y.-S., Xiong, X.-Y., et al: ‘Synthesis, characterisation and in vitro release of paclitaxel-loaded polymeric micelles’, Micro Nano Lett.., 2017, 12, (3), pp. 191–194 (doi: 10.1049/mnl.2016.0690).
17. 17)
  - 2. Gothwal, A., Khan, I., Gupta, U.: ‘Polymeric micelles: recent advancements in the delivery of anticancer drugs’, Pharm. Res., 2016, 33, (1), pp. 18–39 (doi: 10.1007/s11095-015-1784-1).
18. 18)
  - 4. Talelli, M., Barz, M., Rijchen, C.-J.-F., et al: ‘Core-crosslinked polymeric micelles: principles, preparation, biomedical applications and clinical translation’, Nano Today, 2015, 10, (1), pp. 93–117 (doi: 10.1016/j.nantod.2015.01.005).
19. 19)
  - 8. Xu, Z., Liu, S., Liu, H., et al: ‘Unimolecular micelles of amphiphilic cyclodextrin-core star-like block copolymers for anticancer drug delivery’, Chem. Commun., 2015, 51, (87), pp. 15768–15771 (doi: 10.1039/C5CC02743H).
20. 20)
  - 25. Wu, H., Liu, G., Zhang, S., et al: ‘Biocompatibility, MR imaging and targeted drug delivery of a rattle-type magnetic mesoporous silica nanosphere system conjugated with PEG and cancer-cell-specific ligands’, J. Mater. Chem., 2011, 21, (9), pp. 3037–3045 (doi: 10.1039/c0jm02863k).
21. 21)
  - 27. Deming, T.-J.: ‘Synthesis and self-assembly of well-defined block copolypeptides via controlled NCA polymerization’, Adv. Polym. Sci., 2013, 262, pp. 1–38 (doi: 10.1007/12_2013_234).
22. 22)
  - 21. Lalatsa, A., Schätzlein, A.-G., Mazza, M., et al: ‘Amphiphilic poly(L-amino acids)-new materials for drug delivery’, J. Controlled Release, 2012, 161, (2), pp. 523–536 (doi: 10.1016/j.jconrel.2012.04.046).
23. 23)
  - 7. Yang, R., Meng, F., Ma, S., et al: ‘Galactose-decorated cross-linked biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone) block copolymer micelles for enhanced hepatoma-targeting delivery of paclitaxel’, Biomacromolecules, 2011, 12, (8), pp. 3047–3055 (doi: 10.1021/bm2006856).
24. 24)
  - 10. Zhang, W., Li, Y., Liu, L., et al: ‘Amphiphilic toothbrushlike copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) as drug carriers with enhanced properties’, Biomacromolecules, 2010, 11, (5), pp. 1331–1338 (doi: 10.1021/bm100116g).
25. 25)
  - 9. Cao, W., Zhu, L.: ‘Synthesis and unimolecular micelles of amphiphilic dendrimer-like star polymer with various functional surface groups’, Macromolecules, 2011, 44, (6), pp. 1500–1512 (doi: 10.1021/ma1021242).
26. 26)
  - 1. Chao, C., Jiang, Y., Cheng, R., et al: ‘Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: promises, progress and prospects’, Nano Today, 2012, 7, (5), pp. 467–480 (doi: 10.1016/j.nantod.2012.08.005).
27. 27)
  - 18. Chen, G., Wang, L., Cordie, T., et al: ‘Multi-functional self-fluorescent unimolecular micelles for tumor-targeted drug delivery and bioimaging’, Biomaterials, 2015, 47, pp. 41–50 (doi: 10.1016/j.biomaterials.2015.01.006).
28. 28)
  - 16. Guo, J., Hong, H., Chen, G., et al: ‘Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumor-targeted drug delivery and positron emission tomography imaging’, ACS Appl. Mater. Interface, 2014, 6, (24), pp. 21769–21779 (doi: 10.1021/am5002585).

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Polypeptide-based amphiphilic brush copolymers as unimolecular micelles: synthesis, characterisation, and encapsulation study

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