Superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid presenting cell uptake mediated by endocytosis
Source abstract
Abstract
The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with modified surfaces can improve targeted delivery and induce cell death by hyperthermia. The goals of this study were to synthesize and characterize surface modified superparamagnetic poly(methyl methacrylate) with folic acid (FA) prepared by miniemulsion polymerization (MNPsPMMA-FA) and to evaluate their in vitro cytotoxicity and cellular uptake in non-tumor cells, murine fibroblast (L929) cells and tumor cells that overexpressed folate receptor (FR) β, and chronic myeloid leukemia cells in blast crisis (K562). Lastly, hemolysis assays were performed on human red blood cells. MNPsPMMA-FA presented an average mean diameter of 135 nm and a saturation magnetization (Ms) value of 37 emu/g of iron oxide, as well as superparamagnetic behavior. The MNPsPMMA-FA did not present cytotoxicity in L929 and K562 cells. Cellular uptake assays showed a higher uptake of MNPsPMMA-FA than MNPsPMMA in K562 cells when incubated at 37 °C. On the other hand, MNPsPMMA-FA showed a low uptake when endocytosis mechanisms were blocked at low temperature (4 °C), suggesting that the MNPsPMMA-FA uptake was mediated by endocytosis. High concentrations of MNPsPMMA-FA showed hemocompatibility when incubated for 24 h in human red blood cells. Therefore, our results suggest that these carrier systems can be an excellent alternative in targeted drug delivery via FR.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Characterization and Applications of Magnetic Nanoparticles · Iron oxide chemistry and applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (64)
Show source-provided references
1. Abulateefeh SR, Spain SG, Thurecht KJ, Aylott JW, Chan WC, Garnett MC, Alexander C (2011) Thermoresponsive polymer colloids for drug delivery and cancer therapy. Macromol Biosci 1:1722–1734. doi: 10.1002/mabi.20110025210.1002/mabi.201100252 ↗
2. Akbarzadeh A, Samiei M, Davaran S (2012) Magnetic nanoparticles: preparation, physical properties, and applications in biomedicine. Nanoscale Res Lett 7(1):144. doi: 10.1186/1556-276X-7-14410.1186/1556-276X-7-144 ↗
3. Andhariya N, Upadhyay R, Mehta R, Chudasama B (2013) Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin. J Nanopart Res 15:1416. doi: 10.1007/s11051-013-1416-910.1007/s11051-013-1416-9 ↗
4. Arosio P, Orsini F, Piras AN, Sandreschi S, Chiellini F, Corti M, Masa M, Múčková M, Schmidtová L, Ravagli C, Baldi G, Nicolato E, Conti G, Marzola P, Lascialfari A (2015) MR imaging and targeting of human breast cancer cells with folate decorated nanoparticles. RSC Adv 5:39760–39770. doi: 10.1039/C5RA04880J10.1039/C5RA04880J ↗
5. Asua JM (2014) Mapping the morphology of polymer-inorganic nanocomposites synthesized by miniemulsion polymerization. Macromol Chem Phys 215:458–464. doi: 10.1002/macp.20130069610.1002/macp.201300696 ↗
6. Bettencourt A, Almeida AJ (2010) Poly(methyl methacrylate) particulate carriers in drug delivery. J. Microencap. 29(4):353–367. doi: 10.3109/02652048.2011.65150010.3109/02652048.2011.651500 ↗
7. Chandrasekharana P, Maity D, Yong CX, Chuangc KH, Ding J, Feng SS (2011) Vitamin E (D-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate) micelles-superparamagnetic iron oxide nanoparticles for enhanced thermotherapy and MRI. Biomaterials 32(24):5663–5672. doi: 10.1016/j.biomaterials.2011.04.03710.1016/j.biomaterials.2011.04.037 ↗
8. Chen D, Tang Q, Li X, Zhou X, Zang J, Xue W-Q, Xiang J-Y, Guo C-Q (2012a) Biocompatibility of magnetic Fe3 O4 nanoparticles and their cytotoxic effect on MCF-7 cells. J Nanomed 7:4973–4985. doi: 10.2147/IJN.S3514010.2147/IJN.S35140 ↗
9. Chen ML, He YJ, Chen XW, Wang JH (2012b) Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery. Langmuir 28:16469–16476. doi: 10.1021/la303957y10.1021/la303957y ↗
10. Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Eu-Leong Y, Xu HE, Karsten M (2013) Structural basis for molecular recognition of folic acid by folate receptors. Nature 500:486–489. doi: 10.1038/nature1232710.1038/nature12327 ↗
11. Chertok B, Moffat BA, David AE, Yu F, Bergemann C, Ross BD, Yang VC (2008) Iron oxide nanoparticles as a drug delivery vehicle for mri monitored magnetic targeting of brain tumors. Biomaterials 29:487–496. doi: 10.1016/j.biomaterials.2007.08.05010.1016/j.biomaterials.2007.08.050 ↗
12. Collins TJ (2007) ImageJ for microscopy. Biotechniques 43:S25–S30. doi: 10.2144/00011251710.2144/000112517 ↗
13. Crespy D, Landfester K (2010) Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers. Beilstein J Org Chem 6:1132–1148. doi: 10.3762/bjoc.6.13010.3762/bjoc.6.130 ↗
14. Dong S, Cho HJ, Lee WY, Roman M (2014) Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting. Biomacromolecules 15:1560–1567. doi: 10.1021/bm401593n10.1021/bm401593n ↗
15. Dorniani D, Hussein MZB, Kura AU, Fakurazi S, Shaari AH, Zalinah A (2012) Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug delivery. Int J Nanomed 7:5745–5756. doi: 10.2147/IJN.S3574610.2147/IJN.S35746 ↗
16. Duan J, Liu M, Zhang Y, Zhao J, Pan Y, Yang X (2012) Folate-decorated chitosan/doxorubicin poly(butyl)cyanoacrylate nanoparticles for tumor-targeted drug delivery. J Nanopart Res 14:761–77010.1007/s11051-012-0761-4 ↗
17. Fan L-H, Luo Y-L, Chen Y-S, Zhang C-H, Wei Q-B (2009) Preparation and characterization of Fe3O4 magnetic composite microspheres covered by a P(MAH-co-MAA) copolymer. J Nanopart Res 11:449–458. doi: 10.1007/s11051-008-9556-z10.1007/s11051-008-9556-z ↗
18. Feuser PE, Bubniak LS, Santos-Silva MC, Cas Viegas A, Castilho-Fernandes A, Nele M, Ricci-Júnior E, Tedesco AC, Sayer C, Araújo PHH (2015a) Encapsulation of magnetic nanoparticles in poly(methyl methacrylate) by miniemulsion and evaluation of hyperthemia in U87MG cells. Europ J Polym 68:355–365. doi: 10.1016/j.eurpolymj.2015.04.02910.1016/j.eurpolymj.2015.04.029 ↗
19. Feuser PE, Fernades AC, Nele M, Cas Viegas A, Tedesco AC, Ricci-Júnior E, Sayer C, de Araújo PHH (2015b) Simultaneous encapsulation of magnetic nanoparticles and zinc phthalocyanine in poly(methyl methacrylate) nanoparticles by miniemulsion polymerization and in vitro studies. Colloid Surf B 135:357–364. doi: 10.1016/j.colsurfb.2015.07.06710.1016/j.colsurfb.2015.07.067 ↗
20. Feuser PE, Gaspar PC, Jacques AV, Tedesco AC, Santos-Silva MC, Ricci-Júnior E, Sayer C, Araújo PHH (2016) Synthesis of ZnPc loaded poly(methyl methacrylate) nanoparticles via miniemulsion polymerization for photodynamic therapy in leukemic cells. Mater Eng C 60:458–466. doi: 10.1016/j.msec.2015.11.06310.1016/j.msec.2015.11.063 ↗
21. García-Díaz M, Nonell S, Villanueva A, Stockert JC, Cañete M, Casadó M, Mora M, Sagristá ML (2011) Do folate-receptor targeted liposomal photosensitizers enhance photodynamic therapy selectivity? Biochim Biophys Acta 1808:1063–1071. doi: 10.1016/j.bbamem.2010.12.01410.1016/j.bbamem.2010.12.014 ↗
22. Gosavi SS, Gosavi Y, Alla RK (2010) Local and Systemic Effects of Unpolymerised Monomers. Dent Res J (Isfahan) 7(2):82–87
23. Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 25:3995–4021. doi: 10.1016/j.biomaterials.2004.10.01210.1016/j.biomaterials.2004.10.012 ↗
24. He L, Li Z, Fu J, Deng Y, He N, Wang Z, Wang H, Shi Z, Wang Z (2009) Preparation of SiO2/(PMMA/Fe3O4) from monolayer linolenic acid modified Fe3O4 nanoparticles via miniemulsion polymerization. J Biomed Nanotechnol 5(5):596–601. doi: 10.1166/jbn.2009.106510.1166/jbn.2009.1065 ↗
25. He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31(13):3657–3666. doi: 10.1016/j.biomaterials.2010.01.06510.1016/j.biomaterials.2010.01.065 ↗
26. Higuchi WI, Misra J (1962) Physical degradation of emulsions via the molecular diffusion route and the possible prevention thereof. J Pharm Sci 51:459. doi: 10.1002/jps.260051051410.1002/jps.2600510514 ↗
27. International standard: Biological Evaluation of Medical Devices–Part 5 (1992) Tests for Cytotoxicity: in vitro methods. ISO 10993-5
28. Kam NWS, O’Connell M, Wisdom JA, Dai H (2005) Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci 102(33):11600–11605. doi: 10.1073/pnas.050268010210.1073/pnas.0502680102 ↗
29. Kumar CSSR, Mohamad F (2011) Magnetic nanomaterials for hyperthermia-based therapy and controlled drug reléase. Adv Drug Deliv Rev 63(9):789–808. doi: 10.1039/c3ra47542e10.1016/j.addr.2011.03.008 ↗
30. Landfester K (2009) Miniemulsion polymerization and the structure of polymer and hybrid nanoparticles. Ang Chem 48:4488–4507. doi: 10.1002/anie.20090072310.1002/anie.200900723 ↗
31. Landfester K, Mailander V (2013) Nanocapsules with specific targeting and release properties using miniemulsion polymerization. Expert Opin Drug Deliv 10:593–609. doi: 10.1517/17425247.2013.77297610.1517/17425247.2013.772976 ↗
32. Landfester K, Ramires LP (2003) Encapsulated magnetite particles for biomedical application J Phys Condes Matter 15:1345–1361. doi: 10.1088/0953-8984/15/15/30410.1088/0953-8984/15/15/304 ↗
33. Leamon CP, Low PS (1991) Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. Proc Natl Acad Sci 88(13):5572–557610.1073/pnas.88.13.5572 ↗
34. Lee SJ, Shim Y-H, Oh JS, Jeong Y-I, Park IK, Lee HC (2015) Folic-acid-conjugated pullulan/poly(dl-lactide-co-glycolide) graft copolymer nanoparticles for folate-receptor-mediated drug delivery. Nanoscale Res Letters 10:43. doi: 10.1186/s11671-014-0706-110.1186/s11671-014-0706-1 ↗
35. Mahdavian AR, Ashjari M, Mobarakeh HS (2008) Nanocomposite particles with core-shell morphology. I. preparation and characterization of Fe3O4–Poly(butyl acrylate-styrene) particles via miniemulsion polymerization. J Appl Polym Sci 21:1242–1249. doi: 10.1002/app.2872910.1002/app.28729 ↗
36. Mody VV, Cox A, Shah S, Singh A, Bevins W, Parihar H (2014) Magnetic nanoparticle drug delivery systems for targeting tumor. Appl Nanosci 4:385–392. doi: 10.1007/s13204-013-0216-y10.1007/s13204-013-0216-y ↗
37. Mohapatra S, Mallick SK, Kmaiti T, Ghosh SK, Pramanik P (2007) Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells. Nanotechnology 18:385102. doi: 10.1088/0957-4484/18/38/38510210.1088/0957-4484/18/38/385102 ↗
38. Moriyama Y, Narita M, Sato K, Urushiyama M, Koyama S, Hirosawa H, Kishi K, Takahashi M, Takai K, Shibata A (1986) Application of hyperthermia to the treatment of human acute leukemia: purging human leukemic progenitor cells by heat. Blood 67(3):802–80410.1182/blood.V67.3.802.802 ↗
39. Moulin M, Dumontet C, Arrigo A-P (2007) Sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis by hyperthermia. Cancer Lett 250(1):117–127. doi: 10.1016/j.canlet.2006.10.01910.1016/j.canlet.2006.10.019 ↗
40. Nan A, Leistner J, Turcu R (2013) Magnetite–polylactic acid nanoparticles by surface initiated organocatalysis ring opening polymerization. J Nanopart Res 15:186910.1007/s11051-013-1869-x ↗
41. Pan Y-J, Li D, Jin S, Wei C, Wu QY, Guo J, Wang CC (2013) Folate-conjugated poly(N-(2-hydroxypropyl)-methacrylamide-co-methacrylic acid) nanohydrogels with pH/redox dual-stimuli response for controlled drug release. 4:3545, doi: 10.1039/c3py00249g10.1039/c3py00249g ↗
42. Pengcheng D, Huiying Y, Jin Z, Peng L (2013) Folic acid-conjugated temperature and pH dual-responsive yolk/shell microspheres as a drug delivery system. J Mater Chem B 1:5298. doi: 10.1039/c3tb2097510.1039/c3tb20975j ↗
43. Qi H, Ratnam M (2006) Synergistic induction of folate receptor B by all-trans retinoic acid and histone deacetylase inhibitors in acute myelogenous leukemia cells: mechanism and utility in enhancing selective growth inhibition by antifolates. Cancer Res 66:5875–5882. doi: 10.1158/0008-5472.CAN-05-404810.1158/0008-5472.CAN-05-4048 ↗
44. Qiu G, Wang Q, Wang C, Lau W (2007) Polystyrene/Fe3O4 magnetic emulsion and nanocomposite prepared by ultrasonically initiated miniemulsion polymerization. Ultrason Sonochem 14:55–61. doi: 10.1016/j.ultsonch.2006.03.00110.1016/j.ultsonch.2006.03.001 ↗
45. Rastogi V, Yadav P, Bhattacharya SS, Mishra AK, Verma N, Verma A, Pandit JK (2014) Carbon nanotubes: an emerging drug carrier for targeting cancer cells. J Drug Deliv doi: 10.1155/2014/67081510.1155/2014/670815 ↗
46. Romio AP, Rodrigues HH, Peres A, Viegas ADC, Kobitskaya E, Ziener U, Landfester K, Sayer C, Araújo PHH (2013) Encapsulation of magnetic nickel nanoparticles via inverse miniemulsion polymerization. J Appl Polym Sci 129:1426–1433. doi: 10.1002/app.3884010.1002/app.38840 ↗
47. Sahoo B, Sanjana K, Devi P, Banerjee R, Maiti TK, Pramanik P, Dhara D (2013) Thermal and pH responsive polymer-tethered multifunctional magnetic nanoparticles for targeted delivery of anticancer drug. ACS Appl Mater Interfac 5:3884–3893. doi: 10.1021/am400572b10.1021/am400572b ↗
48. Saltan N, Kutlu HM, Hür D, Izcan A, Ridvan S (2011) Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid. Int J Nanomed 6:477–484. doi: 10.2147/IJN.S16803
49. Simioni AR, Primo FL, Rodrigues MMA, Lacava ZGM, Morais PC, Tedesco AC (2007) Binding and photophysical studies of biocompatible magnetic fluid in biological medium and development of magnetic nanoemulsion: a new candidate for cancer treatment. IEE Trans Magn 43(6):2459–2461. doi: 10.1109/TMAG.2007.89412610.1109/TMAG.2007.894126 ↗
50. Sudimack JBA, Lee RJ (2000) Targeted drug delivery via the folate receptor. Ad Drug Deliv Rev 41:147–162. doi: 10.1016/S0169-409X(99)00062-910.1016/S0169-409X(99)00062-9 ↗
51. Van der Heijden JW, Oerlemans R, Dijkmans BAC, Qi H, Van der Laken CJ, Lems WF, Jackman AL, Kraan MC, Tak PP, Ratnam M, Jansen G (2009) Folate receptor as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients. Arthritis Rheum 60:12–21. doi: 10.1002/art.2421910.1002/art.24219 ↗
52. Wang JJ, Liu K, Sung K, Tsai C, Fang JY (2009) Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection. Eur J Pharm Sci 38(2):138–146. doi: 10.1016/j.ejps.2009.06.00810.1016/j.ejps.2009.06.008 ↗
53. Wibowo SA, Singh M, Reeder KM, Carter JJ, Kovach AR, Menga W, Ratnam M, Zhang F III, Dann CE (2013) Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci USA 110(38):15180–15188. doi: 10.1073/pnas.130882711010.1073/pnas.1308827110 ↗
54. Xu C, Su S (2013) New forms of superparamagnetic nanoparticles for biomedical applications. Adv Drug Deliv Rev 65:732–743. doi: 10.1016/j.addr.2012.10.00810.1016/j.addr.2012.10.008 ↗
55. Yan F, Li J, Zhang J, Liu F, Yang W (2011) Preparation of Fe3O4/polystyrene composite particles from monolayer oleic acid modified Fe3O4 nanoparticles via miniemulsion polymerization. J Nanopart Res 11:289–296. doi: 10.1007/s11051-008-9382-310.1007/s11051-008-9382-3 ↗
56. Yang H, Li Y, Li T, Xu M, Chen Y, Wu C, Dang X, Liu Y (2014a) Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer. Sci Rep 4:7072. doi: 10.1038/srep0707210.1038/srep07072 ↗
57. Yang Y, Guo X, Wei K, Wang L, Yang D, Lai L, Cheng M, Liu Q (2014b) Synthesis and drug-loading properties of folic acid-modified superparamagnetic Fe3O4 hollow microsphere core/mesoporous SiO2 shell composite particles. J Nanop Res 16(2210):1–10. doi: 10.1007/s11051-013-2210-410.1007/s11676-014-0428-3 ↗
58. Yu T, Malugin A, Ghandehari H (2011) Impact of silica nanoparticle design on cellular toxicity and hemolytic activity. ACS Nano 5(7):5717–5728. doi: 10.1021/nn201390410.1021/nn2013904 ↗
59. Zhang JL, Srivastava RS, Misra RDK (2007) Core-shell magnetite nanoparticles surface encapsulated with smart stimuli-responsive polymer: synthesis, characterization, and LCST of viable drug-targeting delivery system. Langmuir 23(11):6342–6351. doi: 10.1021/la063619910.1021/la0636199 ↗
60. Zhang J, Jiaxin L, Razavi FS, Mumin AM (2011) One-pot synthesis and characterization of rhodamine derivative-loaded magnetic core–shell nanoparticles. J Nanopart Res 13:1909–1916. doi: 10.1007/s11051-010-9942-110.1007/s11051-010-9942-1 ↗
61. Zhao DL, Zhang HL, Zeng XW, Xia QS, Tang JT (2013) Inductive heat property of Fe3O4/polymer composite nanoparticles in an AC magnetic field for localized hyperthermia. Biomed Mater 1:198–201. doi: 10.1088/1748-6041/1/4/00410.1088/1748-6041/1/4/004 ↗
62. Zheng W, Gao F, Gu H (2005) Magnetic polymer nanospheres with high and uniform magnetite content. J Magn Magn Mater 288:403–410. doi: 10.1016/j.jmmm.2004.09.12510.1016/j.jmmm.2004.09.125 ↗
63. Zheng N, YinL Song Z, Ma L, Tang H, Gabrielson NP, Lu H, Cheng J (2014) Maximizing gene delivery efficiencies of cationic helical polypeptides via balanced membrane penetration and cellular targeting. Biomaterials 35:1302–1314. doi: 10.1016/j.biomaterials.2013.09.09010.1016/j.biomaterials.2013.09.090 ↗
64. Zhou Q, Zhang Z, Chen T, Guo X, Xhou S (2011) Preparation and characterization of thermosensitive pluronic F127-b-poly(caprolactone) mixed micelles. Colloid Surf B 86(1):45–47. doi: 10.1016/j.colsurfb.2011.03.01310.1016/j.colsurfb.2011.03.013 ↗