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Molecularly imprinted polymers synthesized using reduction-cleavable hyperbranched polymers for doxorubicin hydrochloride with enhanced loading properties and controlled release

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Abstract

In this contribution, we reported a novel strategy to synthesize porous molecularly imprinted polymers (MIPs) of anticancer drug of doxorubicin hydrochloride (DOX) using reduction-cleavable hyperbranched polymers containing disulfide bonds (ds-HP-alkyne). The porous MIPs (MIP-DOX-HP) possess enhanced specific surface area and porosity by the incorporation of cleavable hyperbranched polymers from the copper(I)–catalyzed azide–alkyne click chemistry. In comparison to MIPs synthesized without using ds-HP-alkyne, MIP-DOX-HP exhibits more regular and open porous structures, which increase the loading and controlled release abilities of DOX anticancer drug. Under optimized pH condition, the total cumulative release amount of DOX at equilibrium is as high as 2134 and 1249 µg for MIP-DOX-HP and MIP-DOX, respectively. The effective and robust strategy for synthesizing MIPs using cleavable hyperbranched polymers is helpful for extending applications of MIPs in drug delivery and target-activated release systems.

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References

  1. Suksaeree J, Pichayakorn W, Monton C et al (2014) Polymers for transdermal drug delivery systems. Ind Eng Chem Res 53:507–513

    Article  Google Scholar 

  2. del Valle EMM, Galan MA, Carbonell RG (2009) Drug delivery technologies: the way forward in the new decade. Ind Eng Chem Res 48:2475–2486

    Article  Google Scholar 

  3. Kompella UB, Amrite AC, Ravi RP, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198

    Article  Google Scholar 

  4. Ma X, Zhou Z, Jin E, Sun Q, Zhang B, Tang J, Shen Y (2013) Facile synthesis of polyester dendrimers as drug delivery carriers. Macromolecules 46:37–42

    Article  Google Scholar 

  5. Guse C, Koennings S, Kreye F, Siepmann F, Goepferich A, Siepmann J (2006) Drug release from lipid-based implants: elucidation of the underlying mass transport mechanisms. Int J Pharm 314:137–144

    Article  Google Scholar 

  6. Ha W, Yu J, Song XY, Zhang ZJ, Liu YQ, Shi YP (2013) Prodrugs forming multifunctional supramolecular hydrogels for dual cancer drug delivery. J Mater Chem B 1:5532–5538

    Article  Google Scholar 

  7. Lu CH, Zhou WH, Han B, Yang HH, Chen X, Wang XR (2007) Surface-imprinted core-shell nanoparticles for sorbent assays. Anal Chem 79:5457–5461

    Article  Google Scholar 

  8. Schirhagl R (2014) Bioapplications for molecularly imprinted polymers. Anal Chem 86:250–261

    Article  Google Scholar 

  9. Svenson J, Nicholls IA (2001) On the thermal and chemical stability of molecularly imprinted polymers. Anal Chim Acta 435:19–24

    Article  Google Scholar 

  10. Zhu T, Xu D, Wu Y, Li J, Zhou M, Tian T, Jiang Y, Li F, Li G (2013) Surface molecularly imprinted electrospun affinity membranes with multimodal pore structures for efficient separation of proteins. J Mater Chem B 1:6449–6458

    Article  Google Scholar 

  11. Tong K, Xiao S, Li S, Wang J (2008) Molecular recognition and catalysis by molecularly imprinted polymer catalysts: thermodynamic and kinetic surveys on the specific behaviors. J Inorg Organomet Polym Mater 18:426–433

    Article  Google Scholar 

  12. Liu S, Yan H, Wang M, Wang L (2013) Water-compatible molecularly imprinted microspheres in pipette tip solid-phase extraction for simultaneous determination of five fluoroquinolones in eggs. J Agric Food Chem 61:11974–11980

    Article  Google Scholar 

  13. Ansell RJ, Kuah JKL, Wang D, Jackson CE, Bartle KD, Clifford AA (2012) Imprinted polymers for chiral resolution of (±)-ephedrine, 4: packed column supercritical fluid chromatography using molecularly imprinted chiral stationary phases. J Chromatogr A 1264:117–123

    Article  Google Scholar 

  14. Lulinski P (2010) Molecular imprinted polymers in pharmaceutical sciences. Polimery 55:799–805

    Google Scholar 

  15. Puoci F, Iemma F, Cirillo G, Picci N, Matricardi P, Alhaique F (2007) Molecularly imprinted polymers for 5-fluorouracil release in biological fluids. Molecules 12:805–814

    Article  Google Scholar 

  16. Dramou P, Zuo P, He H, Lien Ai PH, Zou W, Xiao D, Chuong PH, Ndorbor T (2013) Anticancer loading and controlled release of novel water-compatible magnetic nanomaterials as drug delivery agents, coupled to a computational modeling approach. J Mater Chem B 1:4099–4109

    Article  Google Scholar 

  17. Parisi OI, Morelli C, Puoci F, Saturnino C, Caruso A, Sisci D, Trombino GE, Picci N, Sinicropi MS (2014) Magnetic molecularly imprinted polymers (MMIPs) for carbazole derivative release in targeted cancer therapy. J Mater Chem B 2:6619–6625

    Article  Google Scholar 

  18. Chen L, Xu S, Li J (2011) Recent advances in molecular imprinting technology: current status, challenges and highlighted applications. Chem Soc Rev 40:2922–2942

    Article  Google Scholar 

  19. He Y, Huang Y, Jin Y, Liu X, Liu G, Zhao R (2014) Well-defined nanostructured surface-imprinted polymers for highly selective magnetic separation of fluoroquinolones in human urine. ACS Appl Mat Interfaces 6:9634–9642

    Article  Google Scholar 

  20. Zhu XY, Zhou YF, Yan DY (2011) Influence of branching architecture on polymer properties. J Polym Sci Part B 49:1277–1286

    Article  Google Scholar 

  21. Wu WB, Qin JG, Li Z (2013) New design strategies for second-order nonlinear optical polymers and dendrimers. Polymer 54:4351–4382

    Article  Google Scholar 

  22. Chen H, Kong J (2016) Hyperbranched polymers from A2+B3 Strategy: recent advances in description and control of fine topology. Polym Chem 7:3643–3663

    Article  Google Scholar 

  23. Kong J, Wang MJ, Zou JH, An LN (2015) Soluble and meltable hyperbranched polyborosilazanes towards high-temperature stable SiBCN ceramics. ACS Appl Mater Interfaces 7:6733–6744

    Article  Google Scholar 

  24. Chen H, Kong J, Tian W, Fan XD (2012) Intramolecular cyclization in A2+B3 polymers prepared by step-wise polymerization resulting in a highly branched topology: quantitative determination of cycles by combined NMR and SEC analytics. Macromolecules 45:6185–6195

    Article  Google Scholar 

  25. Smeets NMB (2013) Amphiphilic hyperbranched polymers from the copolymerization of a vinyl and divinyl monomer: the potential of catalytic chain transfer polymerization. Eur Polym J 49:2528–2544

    Article  Google Scholar 

  26. Schuell C, Frey H (2013) Grafting of hyperbranched polymers: from unusual complex polymer topologies to multivalent surface functionalization. Polymer 54:5443–5455

    Article  Google Scholar 

  27. Wurm F, Frey H (2012) Hyperbranched polymers: synthetic methodology, properties, and complex polymer architectures. Polym Sci 6:177–198

    Google Scholar 

  28. Yao B, Mei J, Li J, Wang J, Wu H, Sun JZ, Qin A, Tang BZ (2014) Catalyst-free thiol-yne click polymerization: a powerful and facile tool for preparation of functional poly(vinylene sulfide)s. Macromolecules 47:1325–1333

    Article  Google Scholar 

  29. Zhao F, Yin H, Zhang Z, Li J (2013) Folic acid modified cationic gamma-cyclodextrin -oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery. Biomacromolecules 14:476–484

    Article  Google Scholar 

  30. Li L, Wang X, Yang J, Ye X, Wu C (2014) Degradation kinetics of model hyperbranched chains with uniform subchains and controlled locations of cleavable disulfide linkages. Macromolecules 47:650–658

    Article  Google Scholar 

  31. Tang LY, Wang YC, Li Y, Du JZ, Wang J (2009) Shell-detachable micelles based on disulfide-linked block copolymer as potential carrier for intracellular drug delivery. Bioconj Chem 20:1095–1099

    Article  Google Scholar 

  32. Wang F, Wang YC, Dou S, Xiong MH, Sun TM, Wang J (2011) Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano 5:3679–3692

    Article  Google Scholar 

  33. Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S (2009) Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery. Biomaterials 30:5757–5766

    Article  Google Scholar 

  34. Wan D, Ohta S, Kakuchi T, Satoh T (2011) A hydrophilic unimolecular nanocapsule with cyclodextrin moieties in the core: chemically triggered on-demand release and pH-response. Soft Matter 7:6422–6425

    Article  Google Scholar 

  35. Jiang L, Gao ZM, Ye L, Zhang AY, Feng ZG (2013) A tumor-targeting nano doxorubicin delivery system built from amphiphilic polyrotaxane-based block copolymers. Polymer 54:5188–5198

    Article  Google Scholar 

  36. Xie XY, Pan XY, Han SL, Wang SC (2015) Development and characterization of magnetic molecularly imprinted polymers for the selective enrichment of endocrine disrupting chemicals in water and milk samples. Anal Bioanal Chem 407:1735–1744

    Article  Google Scholar 

  37. Shen X, Ye L (2011) Interfacial molecular imprinting in nanoparticle-stabilized emulsions. Macromolecules 44:5631–5637

    Article  Google Scholar 

  38. Molina EF, Parreira RLT, De Faria EH, de Carvalho HWP, Caramori GF, Coimbra DF, Nassar EJ, Ciuffi KJ (2014) Ureasil-poly(ethylene oxide) hybrid matrix for selective adsorption and separation of dyes from water. Langmuir 30:3857–3868

    Article  Google Scholar 

  39. Zhou Y, Huang W, Liu J, Zhu X, Yan D (2010) Self-ssembly of hyperbranched polymers and its biomedical applications. Adv Mater 22:4567–4590

    Article  Google Scholar 

  40. Chen H, Kong J (2014) Terminal index: a new way for precise description of topologic structure of highly branched polymers derived from A2+B3 stepwise polymerization. J Phys Chem B 118:3441–3450

    Article  Google Scholar 

  41. Chen H, Zhang S, Kong J (2015) Topological analysis and intramolecular cyclic feature evaluation of highly branched polymers derived from Am+Bn step-growth polymerization. Polym Chem 6:909–916

    Article  Google Scholar 

  42. Yang KG, Liu ZB, Mao M, Zhang XH, Zhao CS, Nishi N (2005) Molecularly imprinted polyethersulfone microspheres for the binding and recognition of bisphenol A. Anal Chim Acta 546:30–36

    Article  Google Scholar 

  43. Zhao WF, Tang YS, Xi J, Kong J (2015) Covalent functionalization of chemically-converted graphene sheets with poly(ionic liquid)s and high adsorption capacity of anionic dyes. Appl Surf Sci 326:276–284

    Article  Google Scholar 

  44. Meng LL, Zhang XF, Tang YS, Su KH, Kong J (2015) Hierarchically porous silicon-carbon-nitrogen hybrid materials towards highly efficient and selective adsorption of organic dyes. Sci Rep 5:7910

    Article  Google Scholar 

  45. Yilmaz E, Mosbach K, Haupt K (1999) Influence of functional and cross-linking monomers and the amount of template on the performance of molecularly imprinted polymers in binding assays. Anal Commun 36:167–170

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21404085/21374089) and Science Foundation of Northwest University (13NW22). J.K. acknowledges the support from New Century Excellent Talents of the Education Ministry of China (NCET-11-0817).

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Authors and Affiliations

  1. Key Laboratory of Synthetic and Natural Functional Molecular Chemistry, College of Chemistry and Materials Science, Northwest University, Xi’an, 710069, People’s Republic of China

    Fangfang Chen

  2. MOE Key Laboratory of Space Applied Physics and Chemistry, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of China

    Fangfang Chen, Heng Chen, Xiao Duan, Jiqiong Jia & Jie Kong

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  1. Fangfang Chen
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Correspondence to Jie Kong.

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Chen, F., Chen, H., Duan, X. et al. Molecularly imprinted polymers synthesized using reduction-cleavable hyperbranched polymers for doxorubicin hydrochloride with enhanced loading properties and controlled release. J Mater Sci 51, 9367–9383 (2016). https://doi.org/10.1007/s10853-016-0183-2

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