Advertisement

pH-responsive polymeric micelles with tunable aggregation-induced emission and controllable drug release

  • Yu Dai
  • Dengjin Wu
  • Shijun Lin
  • Xin Ma
  • Xiaojin ZhangEmail author
  • Fan XiaEmail author
Research Paper
  • 44 Downloads

Abstract

Stimuli-responsive polymeric micelles as a drug delivery vehicle have made important contributions to the development of controllable drug release. Here we develop pH-responsive polymeric micelles with tunable aggregation-induced emission and controllable drug release. Polymeric micelles in nano-sized spherical shape (about 140 nm) were mediated via hydrogen-bonding interaction between phenol groups of 4,4′-(1,2-diphenylethene-1,2-diyl)diphenol (TPE-2OH) and amine groups of poly(ethylene glycol)-block-linear polyethylenimine-block-poly(ε-caprolactone) (PEG-PEI-PCL). The results show that polymeric micelles are pH-responsive with turn-on fluorescence and sustained drug release inside cells, which has hope in simultaneously achieving cell imaging and cancer therapy.

Keywords

pH-responsive polymeric micelles Hydrogen-bonding interaction Aggregation-induced emission Drug release Self-assembly Biomaterials Nanomedicine 

Notes

Funding

This work was financially supported by the National Natural Science Foundation of China (Nos. 21603196, 51703209, and 21525523), the Natural Science Foundation of Hubei Province (2017CFB217), and the Fundamental Research Funds for the Central Universities, China University of Geosciences (Wuhan) (Nos. CUG170601 and CUGL170406).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

11051_2018_4447_MOESM1_ESM.docx (364 kb)
ESM 1 (DOCX 363 kb)

References

  1. Bains A, Wulff JE, Moffitt MG (2016) Microfluidic synthesis of dye-loaded polycaprolactone-block-poly (ethylene oxide) nanoparticles: insights into flow-directed loading and in vitro release for drug delivery. J Colloid Interface Sci 475:136–148.  https://doi.org/10.1016/j.jcis.2016.04.010 CrossRefGoogle Scholar
  2. Boussif O, Lezoualch F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 92:7297–7301.  https://doi.org/10.1073/pnas.92.16.7297 CrossRefGoogle Scholar
  3. Breunig M, Lungwitz U, Liebl R, Goepferich A (2007) Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc Natl Acad Sci U S A 104:14454–14459.  https://doi.org/10.1073/pnas.0703882104 CrossRefGoogle Scholar
  4. Chen Q, Lin WJ, Wang HY, Wang JF, Zhang LJ (2016) PDEAEMA-based pH-sensitive amphiphilic pentablock copolymers for controlled anticancer drug delivery. RSC Adv 6:68018–68027.  https://doi.org/10.1039/c6ra10757e CrossRefGoogle Scholar
  5. Dai Y, Li Y, Wang SP (2015) ABC triblock copolymer-stabilized gold nanoparticles for catalytic reduction of 4-nitrophenol. J Catal 329:425–430.  https://doi.org/10.1016/j.jcat.2015.06.006 CrossRefGoogle Scholar
  6. Dai Y, Yu P, Zhang XJ, Zhuo RX (2016a) Gold nanoparticles stabilized by amphiphilic hyperbranched polymers for catalytic reduction of 4-nitrophenol. J Catal 337:65–71.  https://doi.org/10.1016/j.jcat.2016.01.014 CrossRefGoogle Scholar
  7. Dai Y, Zhang XJ, Zhuo RX (2016b) Amphiphilic linear-hyperbranched polymer poly(ethylene glycol) -branched polyethylenimine-poly(ε-caprolactone): synthesis, self-assembly and application as stabilizer of platinum nanoparticles. Polym Int 65:691–697.  https://doi.org/10.1002/pi.5118 CrossRefGoogle Scholar
  8. Dai Y, Zhang XJ, Zhuo RX (2016c) Polymeric micelles stabilized by polyethylenimine-copper (C2H5N-Cu) coordination for sustained drug release. RSC Adv 6:22964–22968.  https://doi.org/10.1039/c6ra02300b CrossRefGoogle Scholar
  9. de Luzuriaga AR, Garcia I, Mecerreyes D, Etxeberria A, Pomposo JA (2010) Design and stabilization of block copolymer micelles via phenol-pyridine hydrogen-bonding interactions. Polymer 51:1355–1362.  https://doi.org/10.1016/j.polymer.2010.01.032 CrossRefGoogle Scholar
  10. Deshmukh AS et al (2017) Polymeric micelles: basic research to clinical practice. Int J Pharm 532:249–268.  https://doi.org/10.1016/j.ijpharm.2017.09.005 CrossRefGoogle Scholar
  11. Di Maria F, Blasi L, Quarta A, Bergamini G, Barbarella G, Giorgini L, Benaglia M (2015) New biocompatible polymeric micelles designed for efficient intracellular uptake and delivery. J Mater Chem B 3:8963–8972.  https://doi.org/10.1039/c5tb01631b CrossRefGoogle Scholar
  12. Fang Y, Liu L, Feng Y, Li XS, Guo QX (2002) Effects of hydrogen bonding to amines on the phenol/phenoxyl radical oxidation. J Phys Chem A 106:4669–4678.  https://doi.org/10.1021/jp014425z CrossRefGoogle Scholar
  13. Ge ZS, Liu SY (2013) Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem Soc Rev 42:7289–7325.  https://doi.org/10.1039/c3cs60048c CrossRefGoogle Scholar
  14. Huh KM, Kang HC, Lee YJ, Bae YH (2012) pH-sensitive polymers for drug delivery. Macromol Res 20:224–233.  https://doi.org/10.1007/s13233-012-0059-5 CrossRefGoogle Scholar
  15. Kim D, Lee ES, Oh KT, Gao ZG, Bae YH (2008) Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH. Small 4:2043–2050.  https://doi.org/10.1002/smll.200701275 CrossRefGoogle Scholar
  16. Kuang HH, Wu SH, Meng FB, Xie ZG, Jing XB, Huang YB (2012) Core-crosslinked amphiphilic biodegradable copolymer based on the complementary multiple hydrogen bonds of nucleobases: synthesis, self-assembly and in vitro drug delivery. J Mater Chem 22:24832–24840.  https://doi.org/10.1039/c2jm34852g CrossRefGoogle Scholar
  17. Li TZ et al (2016) Thermoresponsive AIE polymers with fine-tuned response temperature. J Mater Chem C 4:2964–2970.  https://doi.org/10.1039/c5tc03298a CrossRefGoogle Scholar
  18. Liu J, Huang YR, Kumar A, Tan A, Jin SB, Mozhi A, Liang XJ (2014) pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol Adv 32:693–710.  https://doi.org/10.1016/j.biotechadv.2013.11.009 CrossRefGoogle Scholar
  19. Luo JD , Xie Z, Lam JWY, Cheng L, Tang BZ, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu Det al. (2001) Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole Chem Commun:1740–-1741 doi: https://doi.org/10.1039/b105159h
  20. Min K, Choi W, Kim C, Choi M (2018) Oxidation-stable amine-containing adsorbents for carbon dioxide capture. Nat Commun 9:726.  https://doi.org/10.1038/s41467-018-03123-0 CrossRefGoogle Scholar
  21. Parrott EPJ, Tan NY, Hu RR, Zeitler JA, Tang BZ, Pickwell-MacPherson E (2014) Direct evidence to support the restriction of intramolecular rotation hypothesis for the mechanism of aggregation-induced emission: temperature resolved terahertz spectra of tetraphenylethene. Mater Horiz 1:251–258.  https://doi.org/10.1039/c3mh00078h CrossRefGoogle Scholar
  22. Tarassoli SP et al (2017) Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. Nanotechnology 28:055101.  https://doi.org/10.1088/1361-6528/28/5/055101 CrossRefGoogle Scholar
  23. Tian SD et al (2016) pH-regulated reversible transition between polyion complexes (PIC) and hydrogen-bonding complexes (HBC) with tunable aggregation-induced emission. ACS Appl Mater Interfaces 8:3693–3702.  https://doi.org/10.1021/acsami.5b08970 CrossRefGoogle Scholar
  24. van Meerloo J, Kaspers GJL, Cloos J (2011) Cell sensitivity assays: the MTT assay. Methods Mol Biol 731:237–245.  https://doi.org/10.1007/978-1-61779-080-5_20 CrossRefGoogle Scholar
  25. Wan Q et al (2015) Stimulus responsive cross-linked AIE-active polymeric nanoprobes: fabrication and biological imaging application. Polym Chem 6:8214–8221.  https://doi.org/10.1039/c5py01513h CrossRefGoogle Scholar
  26. Wang Y, Li DD, Wang HB, Chen YJ, Han HJ, Jin Q, Ji J (2014) pH responsive supramolecular prodrug micelles based on cucurbit[8]uril for intracellular drug delivery. Chem Commun 50:9390–9392.  https://doi.org/10.1039/c4cc03978e CrossRefGoogle Scholar
  27. Yang H, Ma RJ, Yue J, Li C, Liu Y, An YL, Shi LQ (2015) A facile strategy to fabricate glucose-responsive vesicles via a template of thermo-sensitive micelles. Polym Chem 6:3837–3846.  https://doi.org/10.1039/c5py00170f CrossRefGoogle Scholar
  28. Yu Y, Zhang H, Cui SX (2011) Fabrication of robust multilayer films by triggering the coupling reaction between phenol and primary amine groups with visible light irradiation. Nanoscale 3:3819–3824.  https://doi.org/10.1039/c1nr10453e CrossRefGoogle Scholar
  29. Zhang XQ et al (2014) A novel method for preparing AIE dye based cross-linked fluorescent polymeric nanoparticles for cell imaging. Polym Chem 5:683–688.  https://doi.org/10.1039/c3py01348k CrossRefGoogle Scholar
  30. Zhang XJ, Mei HJ, Hu C, Zhong ZL, Zhuo RX (2009) Amphiphilic triblock copolycarbonates with poly(glycerol carbonate) as hydrophilic blocks. Macromolecules 42:1010–1016.  https://doi.org/10.1021/ma802350g CrossRefGoogle Scholar
  31. Zhang XJ, Cheng JA, Wang QR, Zhong ZL, Zhuo RX (2010) Miktoarm copolymers bearing one poly(ethylene glycol) chain and several poly(ε-caprolactone) chains on a hyperbranched polyglycerol core. Macromolecules 43:6671–6677.  https://doi.org/10.1021/ma100653u CrossRefGoogle Scholar
  32. Zhang QD, Piro B, Ramsay S, Noel V, Reisberg S, Pham MC (2012) Electrochemical investigation of interactions between quinone derivatives and single stranded DNA. Electrochim Acta 85:588–593.  https://doi.org/10.1016/j.electacta.2012.08.017 CrossRefGoogle Scholar
  33. Zhang XJ, Zhang ZG, Su X, Cai MM, Zhuo RX, Zhong ZL (2013) Phenylboronic acid-functionalized polymeric micelles with a HepG2 cell targetability. Biomaterials 34:10296–10304.  https://doi.org/10.1016/j.biomaterials.2013.09.042 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and ChemistryChina University of GeosciencesWuhanChina

Personalised recommendations