Journal of Ultrafine Grained and Nanostructured Materials

Journal of Ultrafine Grained and Nanostructured Materials

Dual Nano-Carriers using Polylactide-block-Poly(N-isopropylacrylamide-random-acrylic acid) Polymerized from Reduced Graphene Oxide Surface for Doxorubicin Delivery Applications

Document Type : Research Paper

Authors
Leila Khanizadeh 1
Raana Sarvari 2
Bakhshali Massoumi 1
Samira Agbolaghi 3
Younes Beygi-Khosrowshahi 3
1 Department of Chemistry, Payame Noor University, Tehran, Iran.
2 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell And Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Chemical Engineering Department, Faculty of Engineering, Azarbaijan Shahid Madani University, Tabriz, Iran.
10.22059/jufgnsm.2020.01.08
Abstract
The stimuli-responsive nanocomposites were designed as drug delivery nanocarriers. Thanks to promising properties such as large surface area and easy chemical functionalization, the graphene derivatives can be used for the drug delivery applications. For this purpose, in the current work, the poly(L,D-lactide)-block-poly(N-isopropylacrylamide-rand-acrylic acid) grafted from reduced graphene oxide (rGO-graft-PDLA-block-P(NIPAAm-rand-AAc)) was synthesized by thering opening polymerization (ROP) and atom transfer radical polymerization(ATRP). As compared with the traditional radical polymerizations, living polymerizations are among the most-utilized methods to achieve surface initiated polymer brushes as they provide excellent control over the polymers composition. The average sizes of rGO-graft-PDLA-block-P(NIPAAm-rand-AAc) nanocomposite using the dynamic light scattering (DLS) measurements at pH values of 4.0 and 7.4 were 240 and 150 nm, respectively. The lower critical solution temperature (LCST) of rGO-graft-PDLA-block-P(NIPAAm-rand-AAc) was determined to be 39 °C through the ultraviolet-visible (UV-Vis) spectroscopy. The doxorubicin hydrochloride (DOX)-loading capacity was 99 %. The release of DOX increased at 42 °C compared to 37 °C. The results confirmed that the pH- and temperature-dependent releasing of this drug nano-carrier was beneficial for the anticancer at the tumor-like environment. The biocompatibility was also confirmed by assessing the survival rate of breast cancer cell line (MCF7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synthesized nanoparticles would have an excellent potential in the anticancer drug delivery.
Keywords
rGO
NIPAAm
PDLA
graft polymerization
drug delivery
stimuli-responsivity
1. Portney NG, Ozkan M. Nano-oncology: drug delivery, imaging, and sensing. Analytical and Bioanalytical Chemistry. 2006;384(3):620-30.
2. Lomas H, Massignani M, Abdullah KA, Canton I, Lo Presti C, MacNeil S, et al. Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery. Faraday Discussions. 2008;139:143.
3. Gil E, Hudson S. Stimuli-reponsive polymers and their bioconjugates. Progress in Polymer Science. 2004;29(12):1173-222.
4. Zhang X-Z, Yang Y-Y, Chung T-S, Ma K-X. Preparation and Characterization of Fast Response Macroporous Poly(N-isopropylacrylamide) Hydrogels. Langmuir. 2001;17(20):6094-9.
5. Zareie HM, Volga Bulmus E, Gunning AP, Hoffman AS, Piskin E, Morris VJ. Investigation of a stimuli-responsive copolymer by atomic force microscopy. Polymer. 2000;41(18):6723-7.
6. Seo HI, Cheon YA, Chung BG. Graphene and thermo-responsive polymeric nanocomposites for therapeutic applications. Biomedical Engineering Letters. 2016;6(1):10-5.
7. Namvari M, Biswas CS, Galluzzi M, Wang Q, Du B, Stadler FJ. Reduced graphene oxide composites with water soluble copolymers having tailored lower critical solution temperatures and unique tube-like structure. Scientific reports. 2017;7:44508-.
8. Schmaljohann D. Thermo- and pH-responsive polymers in drug delivery☆. Advanced Drug Delivery Reviews. 2006;58(15):1655-70.
9. Kanamala M, Wilson WR, Yang M, Palmer BD, Wu Z. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials. 2016;85:152-67.
10. de las Heras Alarcon C, Pennadam S, Alexander C. Stimuli Responsive Polymers for Biomedical Applications. ChemInform. 2005;36(26).
11. Jaymand M, Lotfi M, Lotfi R. Functional dendritic compounds: potential prospective candidates for dental restorative materials and in situ re-mineralization of human tooth enamel. RSC Advances. 2016;6(49):43127-46.
12. York A, Kirkland S, McCormick C. Advances in the synthesis of amphiphilic block copolymers via RAFT polymerization: Stimuli-responsive drug and gene delivery☆. Advanced Drug Delivery Reviews. 2008;60(9):1018-36.
13. Bains A, Wulff JE, Moffitt MG. Microfluidic synthesis of dye-loaded polycaprolactone- block -poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery. Journal of Colloid and Interface Science. 2016;475:136-48.
14. Huang J, Zhang H, Yu Y, Chen Y, Wang D, Zhang G, et al. Biodegradable self-assembled nanoparticles of poly (d,l-lactide-co-glycolide)/hyaluronic acid block copolymers for target delivery of docetaxel to breast cancer. Biomaterials. 2014;35(1):550-66.
15. Davaran S, Ghamkhari A, Alizadeh E, Massoumi B, Jaymand M. Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis, “schizophrenic” micellization, and its performance as an anticancer drug delivery nanosystem. Journal of Colloid and Interface Science. 2017;488:282-93.
16. Yang M, Gong S. Immunosensor for the detection of cancer biomarker based on percolated graphene thin film. Chemical Communications. 2010;46(31):5796.
17. Rao CNR, Sood AK, Subrahmanyam KS, Govindaraj A. Graphene: The New Two-Dimensional Nanomaterial. Angewandte Chemie International Edition. 2009;48(42):7752-77.
18. Loh KP, Bao Q, Ang PK, Yang J. The chemistry of graphene. Journal of Materials Chemistry. 2010;20(12):2277.
19. Singh V, Joung D, Zhai L, Das S, Khondaker SI, Seal S. Graphene based materials: Past, present and future. Progress in Materials Science. 2011;56(8):1178-271.
20. Novoselov KS, Geim AK, Morozov SV, Jiang D, Katsnelson MI, Grigorieva IV, et al. Two-dimensional gas of massless Dirac fermions in graphene. Nature. 2005;438(7065):197-200.
21. Geim AK, Novoselov KS. The rise of graphene. Nature Materials. 2007;6(3):183-91.
22. Lee C, Wei X, Kysar JW, Hone J. Measurement of the Elastic Properties and Intrinsic Strength of Monolayer Graphene. Science. 2008;321(5887):385-8.
23. Li X, Li C, Zhu H, Wang K, Wei J, Li X, et al. Hybrid thin films of graphene nanowhiskers and amorphous carbon as transparent conductors. Chemical Communications. 2010;46(20):3502.
24. Mrlík M, Ilčíková M, Plachý T, Pavlínek V, Špitalský Z, Mosnáček J. Graphene oxide reduction during surface-initiated atom transfer radical polymerization of glycidyl methacrylate: Controlling electro-responsive properties. Chemical Engineering Journal. 2016;283:717-20.
25. Novoselov KS, Fal′ko VI, Colombo L, Gellert PR, Schwab MG, Kim K. A roadmap for graphene. Nature. 2012;490(7419):192-200.
26. Bai H, Xu Y, Zhao L, Li C, Shi G. Non-covalent functionalization of graphene sheets by sulfonated polyaniline. Chemical Communications. 2009(13):1667.
27. Fang M, Wang K, Lu H, Yang Y, Nutt S. Covalent polymer functionalization of graphene nanosheets and mechanical properties of composites. Journal of Materials Chemistry. 2009;19(38):7098.
28. Lee SH, Dreyer DR, An J, Velamakanni A, Piner RD, Park S, et al. Polymer Brushes via Controlled, Surface-Initiated Atom Transfer Radical Polymerization (ATRP) from Graphene Oxide. Macromolecular Rapid Communications. 2009;31(3):281-8.
29. Ren L, Wang X, Guo S, Liu T. Functionalization of thermally reduced graphene by in situ atom transfer radical polymerization. Journal of Nanoparticle Research. 2011;13(12):6389-96.
30. Gonçalves G, Marques PAAP, Barros-Timmons A, Bdkin I, Singh MK, Emami N, et al. Graphene oxide modified with PMMA via ATRP as a reinforcement filler. Journal of Materials Chemistry. 2010;20(44):9927.
31. Yang Y, Wang J, Zhang J, Liu J, Yang X, Zhao H. Exfoliated Graphite Oxide Decorated by PDMAEMA Chains and Polymer Particles. Langmuir. 2009;25(19):11808-14.
32. Matyjaszewski K, Xia J. Atom Transfer Radical Polymerization. Chemical Reviews. 2001;101(9):2921-90.
33. Zhu S, Li J, Chen Y, Chen Z, Chen C, Li Y, et al. Grafting of graphene oxide with stimuli-responsive polymers by using ATRP for drug release. Journal of Nanoparticle Research. 2012;14(9).
34. Bastakoti BP, Guragain S, Nakashima K, Yamauchi Y. Stimuli-Induced Core-Corona Inversion of Micelle of Poly(acrylic acid)-block-Poly(N-isopropylacrylamide) and Its Application in Drug Delivery. Macromolecular Chemistry and Physics. 2014;216(3):287-91.
35. Massoumi B, Ghamkhari A, Agbolaghi S. Dual stimuli-responsive poly(succinyloxyethylmethacrylate-b-N-isopropylacrylamide) block copolymers as nanocarriers and respective application in doxorubicin delivery. International Journal of Polymeric Materials and Polymeric Biomaterials. 2017;67(2):101-9.
36. Sarvari R, Sattari S, Massoumi B, Agbolaghi S, Beygi-Khosrowshahi Y, Kahaie-Khosrowshahi A. Composite electrospun nanofibers of reduced graphene oxide grafted with poly(3-dodecylthiophene) and poly(3-thiophene ethanol) and blended with polycaprolactone. Journal of Biomaterials Science, Polymer Edition. 2017;28(15):1740-61.
37. Kimura K, Yanagida Y, Haruyama T, Kobatake E, Aizawa M. Gene expression in the electrically stimulated differentiation of PC12 cells. Journal of Biotechnology. 1998;63(1):55-65.
38. Yang J-H, Lin S-H, Lee Y-D. Preparation and characterization of poly(l-lactide)–graphene composites using the in situ ring-opening polymerization of PLLA with graphene as the initiator. Journal of Materials Chemistry. 2012;22(21):10805.
39. Song W, Zheng Z, Tang W, Wang X. A facile approach to covalently functionalized carbon nanotubes with biocompatible polymer. Polymer. 2007;48(13):3658-63.
40. Seligra PG, Nuevo F, Lamanna M, Famá L. Covalent grafting of carbon nanotubes to PLA in order to improve compatibility. Composites Part B: Engineering. 2013;46:61-8.
41. Liu M, Pu M, Ma H. Preparation, structure and thermal properties of polylactide/sepiolite nanocomposites with and without organic modifiers. Composites Science and Technology. 2012;72(13):1508-14.
42. Chen W, Yan L. Preparation of graphene by a low-temperature thermal reduction at atmosphere pressure. Nanoscale. 2010;2(4):559.
43. Sha J, Gao Y, Wu T, Chen X, Cordie T, Zhao H, et al. Biocompatible graphene nanosheets grafted with poly(2-hydroxyethyl methacrylate) brushes via surface-initiated ARGET ATRP. RSC Advances. 2016;6(42):35641-7.
44. Schilli CM, Zhang M, Rizzardo E, Thang SH, Chong YK, Edwards K, et al. A New Double-Responsive Block Copolymer Synthesized via RAFT Polymerization:  Poly(N-isopropylacrylamide)-block-poly(acrylic acid). Macromolecules. 2004;37(21):7861-6.
45. Massoumi B, Sarvari R, Khanizadeh L, Agbolaghi S, Beygi-Khosrowshahi Y. pH-responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone-block-poly(succinyloxyethylmethacrylate) for doxorubicin release. Journal of the Iranian Chemical Society. 2019;16(9):2031-43.
46. Ghamkhari A, Sarvari R, Ghorbani M, Hamishehkar H. Novel thermoresponsive star-liked nanomicelles for targeting of anticancer agent. European Polymer Journal. 2018;107:143-54.
47. Francis R, Jijil CP, Prabhu CA, Suresh CH. Synthesis of poly(N-isopropylacrylamide) copolymer containing anhydride and imide comonomers – A theoretical study on reversal of LCST. Polymer. 2007;48(22):6707-18.
48. You Y-Z, Oupický D. Synthesis of Temperature-Responsive Heterobifunctional Block Copolymers of Poly(ethylene glycol) and Poly(N-isopropylacrylamide). Biomacromolecules. 2007;8(1):98-105.
49. Guo Y, He W, Yang S, Zhao D, Li Z, Luan Y. Co-delivery of docetaxel and verapamil by reduction-sensitive PEG-PLGA-SS-DTX conjugate micelles to reverse the multi-drug resistance of breast cancer. Colloids and Surfaces B: Biointerfaces. 2017;151:119-27.
50. Song X, Zhu J-l, Wen Y, Zhao F, Zhang Z-X, Li J. Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly(N-isopropylacrylamide) and adamantyl-poly(ethylene glycol). Journal of Colloid and Interface Science. 2017;490:372-9.
51. Emamzadeh M, Desmaële D, Couvreur P, Pasparakis G. Dual controlled delivery of squalenoyl-gemcitabine and paclitaxel using thermo-responsive polymeric micelles for pancreatic cancer. Journal of Controlled Release. 2017;259:e90-e1.
52. Bigot J, Charleux B, Cooke G, Delattre Fo, Fournier D, Lyskawa Jl, et al. Tetrathiafulvalene End-Functionalized Poly(N-isopropylacrylamide): A New Class of Amphiphilic Polymer for the Creation of Multistimuli Responsive Micelles. Journal of the American Chemical Society. 2010;132(31):10796-801.
53. Ghorbani M, Hamishehkar H, Arsalani N, Entezami AA. Surface decoration of magnetic nanoparticles with folate-conjugated poly(N-isopropylacrylamide-co-itaconic acid): A facial synthesis of dual-responsive nanocarrier for targeted delivery of doxorubicin. International Journal of Polymeric Materials and Polymeric Biomaterials. 2016;65(13):683-94.
 
Journal of Ultrafine Grained and Nanostructured Materials
Volume 53, Issue 1
June 2020
Pages 60-70

  • Receive Date 04 June 2019
  • Revise Date 01 June 2020
  • Accept Date 03 June 2020