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Non-cytotoxic poly(amino acid) with excellent thermo-sensitivity from L-lysine and L-aspartic acid as a hydrophobic drug carrier

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Abstract

The thermo-sensitive poly(amino acid)s have aroused great concern due to their good biocompatibility, chirality and multi-functional groups. In this investigation, a group of poly(L-lysine ester -co- N-propionyl-L-aspartic acid)s (PLPA) with excellent thermo-sensitivity and non-cytotoxicity have been successfully synthesized by the polycondensation between α/ε-amino groups of L-lysine and α/γ-carboxyls from L-aspartic acid. The structure and properties of PLPA including monomers are characterized by FTIR, 1H NMR, UV, DSC, GPC, SEM, Contact angle measurement, CCK-8 Cell Counting Kit assess and Confocal laser-scanning microscopy (CLSM). Among four designed PLPAs, only PLPAs possessing methyl/ethyl in the ester moiety show a reversible lower critical solution temperature (LCST) of 21.3–36.2 °C, very close to body temperature. The thermo-sensitivity of PLPAs is strongly affected by the polymer structure, its molecular weight and concentration. The contact angle measurement clearly reveals the effect of pendant groups and temperature on the hydrophlilicity/hydrophobicity of PLPAs. Furthermore, the viability of HeLa cells in 0.01–100 μg/mL PLPA solution is found to be in a range of 90–102% after 24, 48 and 72 h of incubation, indicating its no cytotoxicity. PLPA can facilely form a spherical nano-scale particle with core-shell structure via its thermo-sensitivity. CLSM observations manifest that the curcumin-loaded PLPA particles clearly internalize into the cellular inside. Overall, this noncytotoxic PLPA with excellent thermo-sensitivity is expected to be a promising material in the biomedical fields such as a hydrophobic drug carrier.

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References

  1. Burek M, Czuba PZ, Waskiewicz S (2014). Polymer 55:6460–6470

    Article  CAS  Google Scholar 

  2. Roy D, Camber JN, Sumerlin BS (2009). Prog Polym Sci 35:278–301

    Article  Google Scholar 

  3. Aseyev V, Tenhu H, Winnik FM (2011). Adv Polym Sci 242:29–89

    Article  CAS  Google Scholar 

  4. Shen Y, Fu XH, Fu WX, Li ZB (2015). Chem Soc Rev 44:612–622

    Article  CAS  Google Scholar 

  5. Seuring J, Agarwal S (2012). Macromol Rapid Commun 33:1898–1920

    Article  CAS  Google Scholar 

  6. Shimada N, Ino H, Maie K, Nakayama M, Kano A, Maruyama A (2011). Biomacromolecules 12:3418–3422

    Article  CAS  Google Scholar 

  7. Bagheri M, Shateri S, Niknejad H, Entezami AA (2014). J Polym Res 21:567–581

    Article  Google Scholar 

  8. Asmarandei I, Fundueanu G, Cristea M, Harabagiu V, Constantin M (2013). J Polym Res 20:293–306

    Article  Google Scholar 

  9. Galperin A, Long TJ, Ratner BD (2010). Biomacromolecules 11:2583–2592

    Article  CAS  Google Scholar 

  10. Sopita WI, Thuyen K, Thi N, Wanwipa S, Kwanchanok VP (2013). J Appl Polym Sci 129:3061–3069

    Article  Google Scholar 

  11. Champ S, Xue W, Huglin MB (2011). Polymer 42:6439–6455

    Article  Google Scholar 

  12. Fong RB, Ding ZL, Hoffmanl AS, Stayton PS (2002). Biotechnol Bioeng 79:271–276

    Article  CAS  Google Scholar 

  13. Schappacher M, Putaux JL, Lefebvre C, Deffieux A (2005). J Am Chem Soc 127:2990–2998

    Article  CAS  Google Scholar 

  14. Zhang LF, Liang Y, Meng LZ (2010). Polym Adv Technol 21:720–725

    Article  CAS  Google Scholar 

  15. Suwa K, Wada Y, Kishida A, Akashi M (1997). J Polym Sci Part A Polym Chem 35:3377–3384

    Article  CAS  Google Scholar 

  16. Maeda Y, Nakamura T, Ikeda I (2001). Macromolecules 34:1391–1399

    Article  CAS  Google Scholar 

  17. Gupta NR, Ghute PP, Badiger MV (2011). Carbohydr Polym 83:74–80

    Article  CAS  Google Scholar 

  18. Yang Z, Zhang WQ, Zou JH, Shi WF (2007). Polymer 48:931–938

    Article  CAS  Google Scholar 

  19. He XH, Wu XM, Gao CY, Wang K, Lin SL, Huang W, Xie MR, Yan DY (2011). React Funct Polym 71:544–552

    Article  CAS  Google Scholar 

  20. Lee RS, Chen WH, Huang YT (2010). Polymer 51:5942–5951

    Article  CAS  Google Scholar 

  21. Wang LZ, Wang YS, Chen XN, Cui ZhL DHJ, Ma JX, Fu YT (2008). Int J Ophthal 8:1122–1125

    CAS  Google Scholar 

  22. Sun TL, Qing GY (2011). Adv Mater 23:H57–H77

    Article  CAS  Google Scholar 

  23. Wang YC, Tang LY, Wang J (2009). Biomacromolecules 10:66–73

    Article  CAS  Google Scholar 

  24. Tachibana Y, Kurisawa M, Uyama H, Kakuchi T, Kobayashi S (2003). Chem Commun 7:106–107

    Article  Google Scholar 

  25. Li CM, Tang YQ, Armes SP, Morris CT, Rose SF, Lloyd AW, Lewis AL (2005). Biomacromolecules 6:994–999

    Article  CAS  Google Scholar 

  26. Sun JT, Yu ZQ, Hong CY, Pan CY (2012). Macromol Rapid Commun 33:811–818

    Article  CAS  Google Scholar 

  27. Cho JK, Lee SM, Kim CW, Song SC (2011). J Polym Res 18:701–713

    Article  CAS  Google Scholar 

  28. Geng JL, Li K, Qin W, Ma L, Gurzadyan GG, Tang BZ, Liu B (2013). Small 9:2012–2019

    Article  CAS  Google Scholar 

  29. Peng K, Sun JX, Li YX, Zhang BB, Wang YL, Cao XL, Wang YZ (2014). J Funct Mater 45:14156–14160

    CAS  Google Scholar 

  30. Cheng YL, He CL, Xiao CS, Ding JX, Zhuang XL, Chen XS (2011). Polym Chem 2:2627–2634

    Article  CAS  Google Scholar 

  31. Shen Y, Fu XH, Fu WX, Li ZB (2015). Chem Soc Rev 44:612–622

    Article  CAS  Google Scholar 

  32. Shimokuri T, Kaneko T, Serizawa T, Akashi M (2004). Macromol Biosci 4:407–411

    Article  CAS  Google Scholar 

  33. Ohya Y, Toyohara M, Sasakawa M, Arimura H, Ouchi T (2005). Macromol Biosci S:273–276

    Article  Google Scholar 

  34. Trzcinska R, Szweda D, Rangelov S, Suder P, Silberring J, Dworak A, Trzebicka B (2012). J Polym Sci Part A Polym Chem 50:3104–3115

    Article  CAS  Google Scholar 

  35. Lee BH, Song S-C (2011). J Appl Polym Sci 120:998–1005

    Article  CAS  Google Scholar 

  36. Liu Y, Li C, Wang HY, Zhang X-Z, Zhuo RX (2012). Chem Eur J 18:2297–2304

    Article  CAS  Google Scholar 

  37. Triftaridou AI, Chécot F, Iliopoulos I (2011). Macromol Chem Phys 211:768–777

    Article  Google Scholar 

  38. Li J, He WD, He N, Han SC, Sun XL, Li LY, Zhang BY (2009). J Polym Sci Part A Polym Chem 47:1450–1462

    Article  CAS  Google Scholar 

  39. Nistor MT, Chiriac AP, Nita LE, Neamtu I, Vasile C (2013). Polym Eng Sci 53:2345–2352

    Article  CAS  Google Scholar 

  40. Deng HY, Yin ZM, Jiang T, Liu HM, Fan XY, Wang M, Ma X, Fan ZH, Zheng C, Deng KL (2015). Colloid Polym Sci 293:2341–2348

    Article  CAS  Google Scholar 

  41. Di YY, Ma X, Li CX, Liu HM, Fan XY, Wang M, Deng HY, Jiang T, Yin ZM, Deng KL (2014). Macromol Chem Phys 215:365–371

    Article  CAS  Google Scholar 

  42. Ling J, Wang XQ, You LX, Shen ZQ (2016). J Polym Sci Part A Polym Chem 54:3012–3018

    Article  CAS  Google Scholar 

  43. Tappertzhofen K, Weiser F, Montermann E, Reske-Kunz A, Bros M, Zentel R (2015). Macromol Biosci 15:1159–1173

    Article  CAS  Google Scholar 

  44. Hiraishi T, Kajiyama M, Yamato I, Doi Y (2004). Macromol Biosci 4:330–339

    Article  CAS  Google Scholar 

  45. Hadjichristidis N, Iatrou H, Pitsikalis M, Sakellariou G (2009). Chem Rev 109:5528–5578

    Article  CAS  Google Scholar 

  46. Dimitrov I, Schlaad H (2003). Chem Commun 23:2944–2945

    Article  Google Scholar 

  47. Yan YB, Huang LH, Zhang Q, Zhou H (2015) J Appl Polym Sci https://doi.org/10.1002/APP.41669

  48. Yuan WZ, Zhang JC, Wei JG, Yuan H, Ren J (2011). J Polym Sci Part A Polym Chem 49:4071–4080

    Article  CAS  Google Scholar 

  49. Xun W, Wu DQ, Li ZY, Wang HY, Huang FW, Cheng SX, Zhang XZ, Zhuo RX (2009). Macromol Biosci 9:1219–1226

    Article  CAS  Google Scholar 

  50. Goel A, Kunnumakkara AB, Aggarwal BB (2008). Biochem Pharmacol 75:787–809

    Article  CAS  Google Scholar 

  51. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007). Mol Pharm 4:807–818

    Article  CAS  Google Scholar 

  52. Shahani K, Panyam J (2011). J Pharm Sci 100:2599–2609

    Article  CAS  Google Scholar 

  53. Shome S, Talukdar AD, Choudhury MD, Bhattacharya MK, Upadhyaya H (2016). J Pharm Pharmacol 68:1481–1500

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The research was financially supported by National Natural Science Foundation of China (Grant No: 21274035); Hebei Natural Science Foundation of China (Grant No: B2015201133); Training Program for Innovative Research Team and Leading talent in Hebei Province University (Grant No: LJRC024).

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Author notes

  1. Man Zhao and Zhihui Fan contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Analytical Science and Technology Laboratory of Hebei Province, College of Chemistry & Environmental Science, Hebei University, Baoding, 071002, China

    Man Zhao, Zhihui Fan, Zhen Yang, Junlian Xu, Chang Zheng, Ying Yue, Hongmei Liu & Kuilin Deng

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  1. Man Zhao
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  2. Zhihui Fan
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  3. Zhen Yang
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  4. Junlian Xu
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  5. Chang Zheng
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  6. Ying Yue
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  7. Hongmei Liu
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  8. Kuilin Deng
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Correspondence to Hongmei Liu or Kuilin Deng.

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Zhao, M., Fan, Z., Yang, Z. et al. Non-cytotoxic poly(amino acid) with excellent thermo-sensitivity from L-lysine and L-aspartic acid as a hydrophobic drug carrier. J Polym Res 24, 174 (2017). https://doi.org/10.1007/s10965-017-1329-x

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