Colloid and Polymer Science

, Volume 296, Issue 3, pp 627–636 | Cite as

Temperature and pH dual responsive 2-(dimethylamino)ethanethiol modified starch derivatives via a thiol-yne reaction for drug delivery

  • Kwanghyok Jong
  • Benzhi Ju
  • Jinghai Xiu
  • Ryohua Her
  • Sunil Son
Original Contribution


In this study, a novel type of temperature/pH dual responsive polymer PyHES- DMAET ((2-hydroxy-3-(2-propynyloxy) propyl hydroxyethyl starch (PyHES))-2-(dimethylamino) ethanethiol (DMAET)) was synthesized. First, the temperature-responsive polymer PyHES was prepared via hydrophobic modification of hydroxyl groups in hydroxyethyl starch (HES) with propynylglycidyl ether (PGE) subsequently; pH-responsive tertiary amine group was connected to the propynyl group via a thiol-yne click reaction. Because PyHES-DMAET has pH-responsive amino groups and hydrophobic thioether groups, its aqueous solution exhibits excellent temperature/pH dual sensitivity, i.e., a good transference between the hydrophobic (or self-assembly) and hydrophilic (or swelling) state along as a result of changing temperature/pH values; these properties can be exploited, for hydrophobic drug release. The drug release reached 96% at 37 °C and a pH of 6.5. The drug loading capacity of PyHES-DMAET was increased by increasing the degree of substitution (DS) of the hydrophobic propynyl groups in the PyHES. The highest drug loading capacity for doxorubicin (DOX) achieved in this study was 33 wt%.


Hydroxyethyl starch 2-(dimethylamino)ethanethiol Temperature/pH dual responsive Drug release Thiol-yne reaction 


Funding Information

This work was supported by the National Natural Science Foundation of China (21376041, 21076033, 21536002), Fund for innovative research groups of the National Natural Science Fund Committee of Science (21421005), the Fundamental Research Funds for the Central Universites (No.DUT15ZD224, DUT2016TB12) and Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), State Ethnic Affairs Commission & Ministry of Education, China (KF2015004).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

396_2018_4284_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)


  1. 1.
    Maji T, Banerjee S, Biswas Y, Mandal TK (2015) Dual-stimuli-responsive L -serine-based Zwitter ionic UCST-TypePolymer with tunable thermosensitivity. Macromolecules 48:4957–4966CrossRefGoogle Scholar
  2. 2.
    Zhao Y, Ce S, Yang X, Shen B, Sun Y, Chen Y, Xiaowei X, Sun H, Kui Y, Yang B, Lin Q (2016) pH- and temperature-sensitive hydrogel nanoparticles with dual photoluminescence for bioprobes. ACS Nano 10:5856–5863CrossRefGoogle Scholar
  3. 3.
    Yi L, Terrell JL, Tsao C-Y, Hsuan-Chen W, Javvaji V, Kim E, Yi C, Wang Y, Ulijn RV, Raghavan SR, Rubloff GW, Bentley WE, Payne GF (2012) Biofabricating multifunctional soft matter with enzymes and stimuli-responsive materials. Adv Funct Mater 22:3004–3012CrossRefGoogle Scholar
  4. 4.
    Bogomolova A, Kaberov L, Sedlacek O, Filippov SK, Stepanek P, Král V, Wang XY, Liu SL, Ye XD, Hruby M (2016) Double stimuli-responsive polymer systems: how to use crosstalk between pH- and thermosensitivity for drug depots. Eur Polym J 84:54–64. CrossRefGoogle Scholar
  5. 5.
    Jian-Bo Q, Xu Y-L, Liu J-Y, Zeng J-B, Chen Y-L, Zhou W-Q, Liu J-G (2016) Thermo- and pH-responsive polymer brushes-grafted gigaporous polystyrene microspheres as a high-speed protein chromatography matrix. J Chromatogr A 1441:60–67CrossRefGoogle Scholar
  6. 6.
    Eggers S, Lauterbach F, Abetz V (2016) Synthesis and self-assembly of high molecular weight polystyrene-block-poly[2-(N-morpholino)ethyl methacrylate]: a story about microphase separation, amphiphilicity, and stimuli-responsivity. Polymer 107:357–367. CrossRefGoogle Scholar
  7. 7.
    Jiang J, Ma Y, Cui Z (2017) Smart foams based on dual stimuli-responsive surfactant. Colloids Surf A Physicochem Eng Asp 513:287–291. CrossRefGoogle Scholar
  8. 8.
    Deen GR (2012) Solution properties of water-soluble smart poly(N-acryloyl-N′-ethyl piperazine-co-methyl methacrylate). Polymer 4(4):32–45. CrossRefGoogle Scholar
  9. 9.
    Xiao CS, Cheng YL, Zhang Y, Ding JX, He CL, Zhuang XL (2014) Side chain impacts on pH- and thermo-responsiveness of tertiary amine functionalized polypeptides. J Polym Sci, Part A: PolymChem 52(5):671–679. CrossRefGoogle Scholar
  10. 10.
    Luo C, Wenxin F, Li Z, Zhao B (2016) Multi-responsive polymethacrylamide homopolymers derived from tertiary amine-modified l-alanine. Polymer 10:319–327CrossRefGoogle Scholar
  11. 11.
    Liu M, Hongliang D, Zhang W, Zhai G (2017) Internal stimuli-responsive nanocarriers for drug delivery: design strategies and applications. Mater Sci Eng, C 71:1267–1280. CrossRefGoogle Scholar
  12. 12.
    Liang G, Kong T, Huo Y (2016) Dual thermoresponsive and pH-responsive poly(vinyl alcohol) derivatives: synthesis, Phase Transition Study, and Functional Applications. Macromolecules 49:7478–7489CrossRefGoogle Scholar
  13. 13.
    Patra S, Roy E, Karfa P, Kumar S, Madhuri R, Sharma PK (2015) Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment. ACS Appl Mater Interfaces 7:9235–9246CrossRefGoogle Scholar
  14. 14.
    Bai Y, Zhang Z, Zhang A, Chen L, He C, Zhuang X, Chen X (2012) Novel thermo- and pH-responsive hydroxypropyl cellulose- and poly (l-glutamicacid)-based microgels for oral insulin controlled release. Carbohydr Polym 89(4):1207–1121. CrossRefGoogle Scholar
  15. 15.
    He M, Chu C-C (2013) Dual stimuli responsive glycidyl methacrylate chitosan-quaternary ammonium hybrid hydrogel and its bovine serum albumin release. J Appl Polym Sci 130:3736–3745CrossRefGoogle Scholar
  16. 16.
    Wei Q-B, Luo Y-L, Feng F, Zhang Y-Q, Ma R-X (2013) Synthesis, characterization, and swelling kinetics of ph-responsive and temperature-responsive carboxymethyl chitosan/polyacrylamide hydrogels. J Appl Polym Sci 129:806–814CrossRefGoogle Scholar
  17. 17.
    Alvarez-Lorenzo C, Blanco-Fernandez B, Puga AM, Concheiro A (2013) Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv Drug Deliv Rev 65(9):1148–1171. CrossRefGoogle Scholar
  18. 18.
    Lin M, Kang H, Liu R, Huang Y (2010) Smart assembly behaviors of hydroxypropylcellulose-graft-poly(4-vinylpyridine) copolymers in aqueous solution by thermo and pH stimuli. Langmuir 26:18519–18525CrossRefGoogle Scholar
  19. 19.
    Carreira AS, Gonçalves FAMM, Mendonça PV, Gil MH, Coelho JFJ (2010) Temperature and pH responsive polymers based on chitosan: applications and new graft copolymerization strategies based on living radical polymerization. Carbohydr Polym 80(3):618–630. CrossRefGoogle Scholar
  20. 20.
    Yuan W, Zou H, Shen J (2016) Amphiphilic graft copolymers with ethyl cellulose backbone: synthesis, self-assembly and tunable temperature–CO2 response. Carbohydr Polym 136:216–223. CrossRefGoogle Scholar
  21. 21.
    Xu Y, Benzhi J, Zhang S (2014) Novel pH- and temperature-responsive polymer: tertiary amine starch ether. Carbohydr Polym 114:530–536CrossRefGoogle Scholar
  22. 22.
    Lowe AB (2010) Thiol-ene “click” reactions and recent applications in polymer and materials synthesis. Polym Chem 1(1):17–36. CrossRefGoogle Scholar
  23. 23.
    Lee J, McGrath AJ, Hawker CJ, Kim B-S (2016) pH-tunable thermoresponsive PEO-based functional polymers with pendant amine groups. ACS Macro Lett 5:1391–1396CrossRefGoogle Scholar
  24. 24.
    Wang Y, Heinze T, Zhang K (2016) Stimuli-responsive nanoparticles from ionic cellulose derivatives. Nano 8:648–657Google Scholar
  25. 25.
    Jamróz-Piegza M, Utrata-Wesołek A, Trzebicka B, Dworak A (2006) Hydrophobic modification of high molar mass polyglycidol to thermosensitive polymers. Eur Polym J 42(10):2497–2506. CrossRefGoogle Scholar
  26. 26.
    Kuo C-Y, Don T-M, Hsu S-C, Lee C-F, Chiu W-Y, Huang C-Y (2016) Thermo- and pH-induced self-assembly of P(AA-b-NIPAAm-b-AA) triblock copolymers synthesized via RAFT polymerization. J Polym Sci Part A: Polym Chem 54:1109–1118CrossRefGoogle Scholar
  27. 27.
    Liu S, Armes SP (2003) Synthesis and aqueous solution behavior of pH-responsive schizophrenic diblock copolymer. Langmuir 19(10):4432–4438. CrossRefGoogle Scholar
  28. 28.
    Park HW, Jin H-S, Yang SY, Kim J-D (2009) Tunable phase transition behaviors of pH-sensitive polyaspartamides having various cationic pendant groups. Colloid Polym Sci 287(8):919–926. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kwanghyok Jong
    • 1
    • 2
  • Benzhi Ju
    • 1
  • Jinghai Xiu
    • 1
  • Ryohua Her
    • 2
  • Sunil Son
    • 2
  1. 1.State Key Laboratory of Fine ChemicalsDalian University of TechnologyDalianPeople’s Republic of China
  2. 2.Department of Application ChemistryKim Chaek University of TechnologyPyongyangDemocratic People’s Republic of Korea

Personalised recommendations