Skip to main content
SpringerLink
Log in

Review on the applications of nanoemulsions in cancer theranostics

  • Review
  • Published:
Journal of Materials Research Aims and scope Submit manuscript

Abstract

Nanoemulsions are a colloidal particulate system that offer unique potential for therapy and imaging of disease. Due to their physical and chemical properties, they have gained attention in the field of cancer therapy and imaging. A wide variety of hydrophilic and hydrophobic therapeutic agents can be loaded in the shell and core of particles, while at the same time being able to carry different site-specific antibodies/ligands/peptides for targeting specific types of cancer. Due to significant advancements in cancer theranostics provided by nanoemulsions, this review aims to highlight important types of nanoemulsions that have been developed for cancer therapy and imaging (i.e., theranostics). The different types of synthesis methods and techniques for controlling the size, shape, and structure of emulsions for cancer targeting (i.e., passive and active) will be discussed, with the bioimaging (e.g., through their optical/magnetic/radioactive properties) and therapeutic applications of nanoemulsions emphasized.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. S.K. Nune, P. Gunda, P.K. Thallapally, Y.-Y. Lin, M. Laird Forrest, C.J. Berkland, Nanoparticles for biomedical imaging. Expert Opin. Drug Deliv. 6(11), 1175–1194 (2009)

    Article  CAS  Google Scholar 

  2. X. Han, K. Xu, O. Taratula, K. Farsad, Applications of nanoparticles in biomedical imaging. Nanoscale 11(3), 799–819 (2019)

    Article  CAS  Google Scholar 

  3. J.K. Patra, G. Das, L.F. Fraceto, E.V.R. Campos, R.-T. del Pilar, L.S. Acosta-Torres et al., Nano based drug delivery systems: recent developments and future prospects. J. Nanobiotechnol. 16(1), 1–33 (2018)

    Article  CAS  Google Scholar 

  4. A. Aghebati-Maleki, S. Dolati, M. Ahmadi, A. Baghbanzhadeh, M. Asadi, A. Fotouhi et al., Nanoparticles and cancer therapy: perspectives for application of nanoparticles in the treatment of cancers. J. Cell. Physiol. 235(3), 1962–1972 (2020)

    Article  CAS  Google Scholar 

  5. J.B. Vines, J.-H. Yoon, N.-E. Ryu, D.-J. Lim, H. Park, Gold nanoparticles for photothermal cancer therapy. Front. Chem. 7, 167 (2019)

    Article  CAS  Google Scholar 

  6. G. Von Maltzahn, J.-H. Park, A. Agrawal, N.K. Bandaru, S.K. Das, M.J. Sailor et al., Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Can. Res. 69(9), 3892–3900 (2009)

    Article  CAS  Google Scholar 

  7. E.S. Glazer, S.A. Curley, Non-invasive radiofrequency ablation of malignancies mediated by quantum dots, gold nanoparticles and carbon nanotubes. Ther. Deliv. 2(10), 1325–1330 (2011)

    Article  CAS  Google Scholar 

  8. C.J. Gannon, P. Cherukuri, B.I. Yakobson, L. Cognet, J.S. Kanzius, C. Kittrell et al., Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field. Cancer 110(12), 2654–2665 (2007)

    Article  CAS  Google Scholar 

  9. R.A. Revia, M. Zhang, Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances. Mater. Today 19(3), 157–168 (2016)

    Article  CAS  Google Scholar 

  10. Y. Xu, A. Karmakar, D. Wang, M.W. Mahmood, F. Watanabe, Y. Zhang et al., Multifunctional Fe3O4 cored magnetic-quantum dot fluorescent nanocomposites for RF nanohyperthermia of cancer cells. J. Phys. Chem. C 114(11), 5020–5026 (2010)

    Article  CAS  Google Scholar 

  11. S.M. Janib, A.S. Moses, J.A. MacKay, Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev. 62(11), 1052–1063 (2010)

    Article  CAS  Google Scholar 

  12. M. Liu, R.C. Anderson, X. Lan, P.S. Conti, K. Chen, Recent advances in the development of nanoparticles for multimodality imaging and therapy of cancer. Med. Res. Rev. 40(3), 909–930 (2020)

    Article  Google Scholar 

  13. H. Chen, W. Liang, Y. Zhu, Z. Guo, J. Jian, B.-P. Jiang et al., Supercharged fluorescent protein functionalized water-soluble poly (N-phenylglycine) nanoparticles for highly effective imaging-guided photothermal therapy. Chem. Commun. 54(73), 10292–10295 (2018)

    Article  CAS  Google Scholar 

  14. Q. Zhang, W. Shan, C. Ai, Z. Chen, T. Zhou, X. Lv et al., Construction of multifunctional Fe3O4-MTX@ HBc nanoparticles for MR imaging and photothermal therapy/chemotherapy. Nanotheranostics. 2(1), 87 (2018)

    Article  Google Scholar 

  15. S. Rizzitelli, P. Giustetto, J.C. Cutrin, D.D. Castelli, C. Boffa, M. Ruzza et al., Sonosensitive theranostic liposomes for preclinical in vivo MRI-guided visualization of doxorubicin release stimulated by pulsed low intensity non-focused ultrasound. J. Control. Release 202, 21–30 (2015)

    Article  CAS  Google Scholar 

  16. C. Oerlemans, W. Bult, M. Bos, G. Storm, J.F.W. Nijsen, W.E. Hennink, Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm. Res. 27(12), 2569–2589 (2010)

    Article  CAS  Google Scholar 

  17. H. Xing, K. Hwang, Y. Lu, Recent developments of liposomes as nanocarriers for theranostic applications. Theranostics. 6(9), 1336 (2016)

    Article  CAS  Google Scholar 

  18. Y. Lu, E. Zhang, J. Yang, Z. Cao, Strategies to improve micelle stability for drug delivery. Nano Res. 11(10), 4985–4998 (2018)

    Article  Google Scholar 

  19. Y. Yu, L. Qiu, Optimizing particle size of docetaxel-loaded micelles for enhanced treatment of oral epidermoid carcinoma. Nanomedicine 12(7), 1941–1949 (2016)

    Article  CAS  Google Scholar 

  20. M. Grit, D.J. Crommelin, Chemical stability of liposomes: implications for their physical stability. Chem. Phys. Lipid. 64(1–3), 3–18 (1993)

    Article  CAS  Google Scholar 

  21. D.W. Deamer, J. Bramhall, Permeability of lipid bilayers to water and ionic solutes. Chem. Phys. Lipid. 40(2–4), 167–188 (1986)

    Article  CAS  Google Scholar 

  22. K. Bouchemal, S. Briançon, E. Perrier, H. Fessi, Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation. Int. J. Pharm. 280(1–2), 241–251 (2004)

    Article  CAS  Google Scholar 

  23. N. Anton, T.F. Vandamme, The universality of low-energy nano-emulsification. Int. J. Pharm. 377(1–2), 142–147 (2009)

    Article  CAS  Google Scholar 

  24. T. Trimaille, C. Chaix, T. Delair, C. Pichot, H. Teixeira, C. Dubernet et al., Interfacial deposition of functionalized copolymers onto nanoemulsions produced by the solvent displacement method. Colloid Polym. Sci. 279(8), 784–792 (2001)

    Article  CAS  Google Scholar 

  25. C. Mora-Huertas, H. Fessi, A. Elaissari, Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification–diffusion methods: critical comparison. Adv. Coll. Interface. Sci. 163(2), 90–122 (2011)

    Article  CAS  Google Scholar 

  26. A. Perazzo, V. Preziosi, S. Guido, Phase inversion emulsification: current understanding and applications. Adv. Coll. Interface. Sci. 222, 581–599 (2015)

    Article  CAS  Google Scholar 

  27. J.S. Komaiko, D.J. McClements, Formation of food-grade nanoemulsions using low-energy preparation methods: a review of available methods. Comprehens. Rev. Food Sci. Food Saf. 15(2), 331–352 (2016)

    Article  CAS  Google Scholar 

  28. T. Tadros, P. Izquierdo, J. Esquena, C. Solans, Formation and stability of nano-emulsions. Adv. Coll. Interface. Sci. 108, 303–318 (2004)

    Article  CAS  Google Scholar 

  29. A. Håkansson, M. Rayner, General Principles of Nanoemulsion Formation by High-Energy Mechanical Methods. Nanoemulsions (Elsevier, New York, 2018), pp. 103–139

    Google Scholar 

  30. S. Schultz, G. Wagner, K. Urban, J. Ulrich, High-pressure homogenization as a process for emulsion formation. Chem. Eng. Technol. 27(4), 361–368 (2004)

    Article  CAS  Google Scholar 

  31. J. Peng, W.-J. Dong, L. Li, J.-M. Xu, D.-J. Jin, X.-J. Xia et al., Effect of high-pressure homogenization preparation on mean globule size and large-diameter tail of oil-in-water injectable emulsions. J. Food Drug Anal. 23(4), 828–835 (2015)

    Article  CAS  Google Scholar 

  32. L. Mao, J. Yang, D. Xu, F. Yuan, Y. Gao, Effects of homogenization models and emulsifiers on the physicochemical properties of β-carotene nanoemulsions. J. Dispersion Sci. Technol. 31(7), 986–993 (2010)

    Article  CAS  Google Scholar 

  33. G.M. Whitesides, The origins and the future of microfluidics. Nature 442(7101), 368–373 (2006)

    Article  CAS  Google Scholar 

  34. S.T. Sanjay, W. Zhou, M. Dou, H. Tavakoli, L. Ma, F. Xu et al., Recent advances of controlled drug delivery using microfluidic platforms. Adv. Drug Deliv. Rev. 128, 3–28 (2018)

    Article  CAS  Google Scholar 

  35. S. Uluata, E.A. Decker, D.J. McClements, Optimization of nanoemulsion fabrication using microfluidization: role of surfactant concentration on formation and stability. Food Biophys. 11(1), 52–59 (2016)

    Article  Google Scholar 

  36. L. Bai, D.J. McClements, Development of microfluidization methods for efficient production of concentrated nanoemulsions: comparison of single-and dual-channel microfluidizers. J. Colloid Interface Sci. 466, 206–212 (2016)

    Article  CAS  Google Scholar 

  37. J. Canselier, H. Delmas, A. Wilhelm, B. Abismail, Ultrasound emulsification—an overview. J. Dispersion Sci. Technol. 23(1–3), 333–349 (2002)

    Article  CAS  Google Scholar 

  38. T. Leong, T. Wooster, S. Kentish, M. Ashokkumar, Minimising oil droplet size using ultrasonic emulsification. Ultrason. Sonochem. 16(6), 721–727 (2009)

    Article  CAS  Google Scholar 

  39. T. Delmas, H. Piraux, A.-C. Couffin, I. Texier, F. Vinet, P. Poulin et al., How to prepare and stabilize very small nanoemulsions. Langmuir 27(5), 1683–1692 (2011)

    Article  CAS  Google Scholar 

  40. S. Drozdek, U. Bazylińska, Biocompatible oil core nanocapsules as potential co-carriers of paclitaxel and fluorescent markers: preparation, characterization, and bioimaging. Colloid Polym. Sci. 294(1), 225–237 (2016)

    Article  CAS  Google Scholar 

  41. T.H. Le Kim, H. Jun, J.H. Kim, K. Park, J.S. Kim, Y.S. Nam, Lipiodol nanoemulsions stabilized with polyglycerol-polycaprolactone block copolymers for theranostic applications. Biomater. Res. 21(1), 1–10 (2017)

    Article  CAS  Google Scholar 

  42. S.A. Dragulska, Y. Chen, M.T. Wlodarczyk, M. Poursharifi, P. Dottino, R.V. Ulijn et al., Tripeptide-stabilized oil-in-water nanoemulsion of an oleic acids-platinum (II) conjugate as an anticancer nanomedicine. Bioconjug. Chem. 29(8), 2514–2519 (2018)

    Article  CAS  Google Scholar 

  43. S. Liu, D. Chen, Y. Yuan, X. Zhang, Y. Li, S. Yan et al., Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive chemodrugs. Oncotarget 8(39), 65042 (2017)

    Article  Google Scholar 

  44. L. Hong, J. Zhang, J. Geng, J. Qu, L. Liu, Development of a hydrogen peroxide-responsive and oxygen-carrying nanoemulsion for photodynamic therapy against hypoxic tumors using phase inversion composition method. J. Innov. Opt. Health Sci. 14(02), 2150003 (2021)

    Article  CAS  Google Scholar 

  45. C.E. O’Hanlon, K.G. Amede, R. Meredith, J.M. Janjic, NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging. J. Fluorine Chem. 137, 27–33 (2012)

    Article  CAS  Google Scholar 

  46. S. Ganta, A. Singh, P. Kulkarni, A.W. Keeler, A. Piroyan, R.R. Sawant et al., EGFR targeted theranostic nanoemulsion for image-guided ovarian cancer therapy. Pharm. Res. 32(8), 2753–2763 (2015)

    CAS  Google Scholar 

  47. S.H. Shin, E.-J. Park, C. Min, S.I. Choi, S. Jeon, Y.-H. Kim et al., Tracking perfluorocarbon nanoemulsion delivery by 19F MRI for precise high intensity focused ultrasound tumor ablation. Theranostics. 7(3), 562 (2017)

    Article  CAS  Google Scholar 

  48. D.A. Fernandes, D.D. Fernandes, A. Malik, G.N.W. Gomes, S. Appak-Baskoy, E. Berndl et al., Multifunctional nanoparticles as theranostic agents for therapy and imaging of breast cancer. J. Photochemi. Photobiol. B 218, 112110 (2021)

    Article  CAS  Google Scholar 

  49. S.M. Jafari, D.J. McClements, Nanoemulsions: Formulation, Applications, and Characterization (Academic Press, Cambridge, 2018)

    Google Scholar 

  50. T.J. Wooster, S.C. Moore, W. Chen, H. Andrews, R. Addepalli, R.B. Seymour et al., Biological fate of food nanoemulsions and the nutrients they carry–internalisation, transport and cytotoxicity of edible nanoemulsions in Caco-2 intestinal cells. RSC Adv. 7(64), 40053–40066 (2017)

    Article  CAS  Google Scholar 

  51. M. Faria, K.F. Noi, Q. Dai, M. Björnmalm, S.T. Johnston, K. Kempe et al., Revisiting cell–particle association in vitro: a quantitative method to compare particle performance. J. Control. Release 307, 355–367 (2019)

    Article  CAS  Google Scholar 

  52. Y. Fan, Y. Zhang, W. Yokoyama, J. Yi, Endocytosis of corn oil-caseinate emulsions in vitro: impacts of droplet sizes. Nanomaterials 7(11), 349 (2017)

    Article  CAS  Google Scholar 

  53. K. Li, M. Schneider, Quantitative evaluation and visualization of size effect on cellular uptake of gold nanoparticles by multiphoton imaging-UV/Vis spectroscopic analysis. J. Biomed. Opt. 19(10), 101505 (2014)

    Article  CAS  Google Scholar 

  54. H. Reerink, J.T.G. Overbeek, The rate of coagulation as a measure of the stability of silver iodide sols. Discuss. Faraday Soc. 18, 74–84 (1954)

    Article  CAS  Google Scholar 

  55. B. Zhang, X. Zhou, Y. Miao, X. Wang, Y. Yang, X. Zhang et al., Effect of phosphatidylcholine on the stability and lipolysis of nanoemulsion drug delivery systems. Int. J. Pharm. 583, 119354 (2020)

    Article  CAS  Google Scholar 

  56. B. Halamoda-Kenzaoui, M. Ceridono, P. Urbán, A. Bogni, J. Ponti, S. Gioria et al., The agglomeration state of nanoparticles can influence the mechanism of their cellular internalisation. J. Nanobiotechnol. 15(1), 1–15 (2017)

    Article  CAS  Google Scholar 

  57. S. Murugadoss, F. Brassinne, N. Sebaihi, J. Petry, S.M. Cokic, K.L. Van Landuyt et al., Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo. Part. Fibre Toxicol. 17(1), 1–14 (2020)

    Article  CAS  Google Scholar 

  58. M.K. Ha, Y.J. Shim, T.H. Yoon, Effects of agglomeration on in vitro dosimetry and cellular association of silver nanoparticles. Environ. Sci. Nano 5(2), 446–455 (2018)

    Article  CAS  Google Scholar 

  59. T.F. Tadros, Interfacial Phenomena and Colloid Stability: Industrial Applications. Walter de Gruyter GmbH & Co KG (2015).

  60. T.F. Tadros, Handbook of Colloid and Interface Science. De Gruyter (2017).

  61. S.Y. Tang, S. Manickam, T.K. Wei, B. Nashiru, Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation. Ultrason. Sonochem. 19(2), 330–345 (2012)

    Article  CAS  Google Scholar 

  62. L. Lobo, A. Svereika, Coalescence during emulsification: 2. Role of small molecule surfactants. J. Colloid Interface Sci. 261(2), 498–507 (2003)

    Article  CAS  Google Scholar 

  63. I.M. Lifshitz, V.V. Slyozov, The kinetics of precipitation from supersaturated solid solutions. J. Phys. Chem. Solids 19(1–2), 35–50 (1961)

    Article  Google Scholar 

  64. C. Wagner, Theorie der alterung von niederschlägen durch umlösen (Ostwald-reifung). Zeitschrift für Elektrochemie, Berichte der Bunsengesellschaft für physikalische Chemie. 65(7–8), 581–591 (1961)

    Article  CAS  Google Scholar 

  65. I. Lifshitz, V. Slezov, Kinetics of diffusive decomposition of supersaturated solid solutions. Soviet Phys. JETP. 35(8), 331–339 (1959)

    Google Scholar 

  66. T.J. Wooster, M. Golding, P. Sanguansri, Impact of oil type on nanoemulsion formation and Ostwald ripening stability. Langmuir 24(22), 12758–12765 (2008)

    Article  CAS  Google Scholar 

  67. W. Higuchi, J. Misra, Physical degradation of emulsions via the molecular diffusion route and the possible prevention thereof. J. Pharm. Sci. 51(5), 459–466 (1962)

    Article  CAS  Google Scholar 

  68. M.Y. Koroleva, E.V. Yurtov, Ostwald ripening in macro-and nanoemulsions. Russ. Chem. Rev. 90(3), 293 (2021)

    Article  CAS  Google Scholar 

  69. P. Taylor, R. Ottewill, Ostwald ripening in O/W miniemulsions formed by the dilution of O/W microemulsions. Trends Colloid Interface Sci. VIII, 199–203 (1994).

  70. P. Taylor, R. Ottewill, The formation and ageing rates of oil-in-water miniemulsions. Colloids Surf. A 88(2–3), 303–316 (1994)

    Article  CAS  Google Scholar 

  71. A.M. Djerdjev, J.K. Beattie, Enhancement of ostwald ripening by depletion flocculation. Langmuir 24(15), 7711–7717 (2008)

    Article  CAS  Google Scholar 

  72. S. Nie, Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine 5(4), 523–528 (2010)

    Article  Google Scholar 

  73. R.K. Jain, T. Stylianopoulos, Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7(11), 653–664 (2010)

    Article  CAS  Google Scholar 

  74. H. Hashizume, P. Baluk, S. Morikawa, J.W. McLean, G. Thurston, S. Roberge et al., Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 156(4), 1363–1380 (2000)

    Article  CAS  Google Scholar 

  75. B.J. Berne, R. Pecora, Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics (Courier Corporation, 2000).

  76. D.A. Fernandes, D.D. Fernandes, Y. Li, Y. Wang, Z. Zhang, D. Rousseau et al., Synthesis of stable multifunctional perfluorocarbon nanoemulsions for cancer therapy and imaging. Langmuir 32(42), 10870–10880 (2016)

    Article  CAS  Google Scholar 

  77. D. Su, Y. Hou, C. Dong, J. Ren, Fluctuation correlation spectroscopy and its applications in homogeneous analysis. Anal. Bioanal. Chem. 411(19), 4523–4540 (2019)

    Article  CAS  Google Scholar 

  78. W. Azonano, Reviewing the use of nanoparticle tracking analysis (NTA) for nanomaterial characterization (2015).

  79. D. Weinbuch, S. Zölls, M. Wiggenhorn, W. Friess, G. Winter, W. Jiskoot et al., Micro–flow imaging and resonant mass measurement (archimedes)–complementary methods to quantitatively differentiate protein particles and silicone oil droplets. J. Pharm. Sci. 102(7), 2152–2165 (2013)

    Article  CAS  Google Scholar 

  80. C.M. Maguire, M. Rösslein, P. Wick, A. Prina-Mello, Characterisation of particles in solution–a perspective on light scattering and comparative technologies. Sci. Technol. Adv. Mater. 19(1), 732–745 (2018)

    Article  CAS  Google Scholar 

  81. C. Yang, Measuring Zeta Potential, Methods, in Encyclopedia of Microfluidics and Nanofluidics. ed. by D. Li (Springer, Boston, 2008), pp. 1068–1076

    Chapter  Google Scholar 

  82. J.W. Swan, E.M. Furst, A simpler expression for Henry’s function describing the electrophoretic mobility of spherical colloids. J. Colloid Interface Sci. 388(1), 92–94 (2012)

    Article  CAS  Google Scholar 

  83. D.J. Smith, Characterization of nanomaterials using transmission electron microscopy (2015)

  84. V. Klang, N.B. Matsko, C. Valenta, F. Hofer, Electron microscopy of nanoemulsions: an essential tool for characterisation and stability assessment. Micron 43(2–3), 85–103 (2012)

    Article  CAS  Google Scholar 

  85. J.B. Hall, M.A. Dobrovolskaia, A.K. Patri, S.E. McNeil. Characterization of nanoparticles for therapeutics (2007).

  86. E. Meyer, Atomic force microscopy. Prog. Surf. Sci. 41(1), 3–49 (1992)

    Article  CAS  Google Scholar 

  87. M.B. Kok, A. de Vries, D. Abdurrachim, J.J. Prompers, H. Grüll, K. Nicolay et al., Quantitative 1H MRI, 19F MRI, and 19F MRS of cell-internalized perfluorocarbon paramagnetic nanoparticles. Contrast Media Mol. Imaging 6(1), 19–27 (2011)

    Article  CAS  Google Scholar 

  88. D.A. Fernandes, M.C. Kolios, Near-infrared absorbing nanoemulsions as nonlinear ultrasound contrast agents for cancer theranostics. J. Mol. Liq. 287, 110848 (2019)

    Article  CAS  Google Scholar 

  89. J.D. Dove, P.A. Mountford, T.W. Murray, M.A. Borden, Engineering optically triggered droplets for photoacoustic imaging and therapy. Biomed. Opt. Express 5(12), 4417–4427 (2014)

    Article  Google Scholar 

  90. J. Ahmad, S.R. Mir, K. Kohli, K. Chuttani, A.K. Mishra, A. Panda, et al., Solid-nanoemulsion preconcentrate for oral delivery of paclitaxel: formulation design, biodistribution, and γ scintigraphy imaging. BioMed research international (2014).

  91. A.C. Tedesco, E.P. Silva, C.C. Jayme, H.L. Piva, L.P. Franchi, Cholesterol-rich nanoemulsion (LDE) as a novel drug delivery system to diagnose, delineate, and treat human glioblastoma. Mater. Sci. Eng., C 123, 111984 (2021)

    Article  CAS  Google Scholar 

  92. U. Luesakul, S. Puthong, K. Sansanaphongpricha, N. Muangsin, Quaternized chitosan-coated nanoemulsions: a novel platform for improving the stability, anti-inflammatory, anti-cancer and transdermal properties of Plai extract. Carbohyd. Polym. 230, 115625 (2020)

    Article  CAS  Google Scholar 

  93. R.M. Hathout, T.J. Woodman, Applications of NMR in the characterization of pharmaceutical microemulsions. J. Control. Release 161(1), 62–72 (2012)

    Article  CAS  Google Scholar 

  94. L.-J. Jia, D.-R. Zhang, Z.-Y. Li, F.-F. Feng, Y.-C. Wang, W.-T. Dai et al., Preparation and characterization of silybin-loaded nanostructured lipid carriers. Drug Delivery 17(1), 11–18 (2010)

    Article  CAS  Google Scholar 

  95. S. Jusu, J. Obayemi, A. Salifu, C. Nwazojie, V. Uzonwanne, O. Odusanya et al., Drug-encapsulated blend of PLGA-PEG microspheres: in vitro and in vivo study of the effects of localized/targeted drug delivery on the treatment of triple-negative breast cancer. Sci. Rep. 10(1), 1–23 (2020)

    Article  CAS  Google Scholar 

  96. A.G. Agrawal, A. Kumar, P.S. Gide, Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent. Drug Dev. Ind. Pharm. 41(4), 594–604 (2015)

    Article  CAS  Google Scholar 

  97. E.S. Behbahani, M. Ghaedi, M. Abbaspour, K. Rostamizadeh, Optimization and characterization of ultrasound assisted preparation of curcumin-loaded solid lipid nanoparticles: application of central composite design, thermal analysis and X-ray diffraction techniques. Ultrason. Sonochem. 38, 271–280 (2017)

    Article  CAS  Google Scholar 

  98. F.C. Rossetti, M.C. Fantini, A.R.H. Carollo, A.C. Tedesco, M.V.L.B. Bentley, Analysis of liquid crystalline nanoparticles by small angle X-ray diffraction: evaluation of drug and pharmaceutical additives influence on the internal structure. J. Pharm. Sci. 100(7), 2849–2857 (2011)

    Article  CAS  Google Scholar 

  99. M. Gradzielski, Recent developments in the characterisation of microemulsions. Curr. Opin. Colloid Interface Sci. 13(4), 263–269 (2008)

    Article  CAS  Google Scholar 

  100. J. Wik, K.K. Bansal, T. Assmuth, A. Rosling, J.M. Rosenholm, Facile methodology of nanoemulsion preparation using oily polymer for the delivery of poorly soluble drugs. Drug Deliv. Transl. Res. 10(5), 1228–1240 (2020)

    Article  CAS  Google Scholar 

  101. S. Akhtartavan, M. Karimi, K. Karimian, N. Azarpira, M. Khatami, H. Heli, Evaluation of a self-nanoemulsifying docetaxel delivery system. Biomed. Pharmacother. 109, 2427–2433 (2019)

    Article  CAS  Google Scholar 

  102. J. Gonzales, S. Kossatz, S. Roberts, G. Pirovano, C. Brand, C. Pérez-Medina et al., Nanoemulsion-based delivery of fluorescent PARP inhibitors in mouse models of small cell lung cancer. Bioconjug. Chem. 29(11), 3776–3782 (2018)

    Article  CAS  Google Scholar 

  103. P.K. Bae, J. Jung, B.H. Chung, Highly enhanced optical properties of indocyanine green/perfluorocarbon nanoemulsions for efficient lymph node mapping using near-infrared and magnetic resonance imaging. Nano Convergence. 1(1), 1–10 (2014)

    Article  CAS  Google Scholar 

  104. D.A. Estabrook, A.F. Ennis, R.A. Day, E.M. Sletten, Controlling nanoemulsion surface chemistry with poly (2-oxazoline) amphiphiles. Chem. Sci. 10(14), 3994–4003 (2019)

    Article  CAS  Google Scholar 

  105. E.-H. Lee, J.-K. Kim, J.-S. Lim, S.-J. Lim, Enhancement of indocyanine green stability and cellular uptake by incorporating cationic lipid into indocyanine green-loaded nanoemulsions. Colloids Surf. B 136, 305–313 (2015)

    Article  CAS  Google Scholar 

  106. R. Bouchaala, N. Anton, H. Anton, T. Vandamme, J. Vermot, D. Smail et al., Light-triggered release from dye-loaded fluorescent lipid nanocarriers in vitro and in vivo. Colloids Surf. B 156, 414–421 (2017)

    Article  CAS  Google Scholar 

  107. A.S. Klymchenko, E. Roger, N. Anton, H. Anton, I. Shulov, J. Vermot et al., Highly lipophilic fluorescent dyes in nano-emulsions: towards bright non-leaking nano-droplets. RSC Adv. 2(31), 11876–11886 (2012)

    Article  CAS  Google Scholar 

  108. U. Bazylińska, J. Pietkiewicz, J. Saczko, M. Nattich-Rak, J. Rossowska, A. Garbiec et al., Nanoemulsion-templated multilayer nanocapsules for cyanine-type photosensitizer delivery to human breast carcinoma cells. Eur. J. Pharm. Sci. 47(2), 406–420 (2012)

    Article  CAS  Google Scholar 

  109. Q. Wu, R. Xia, C. Li, Y. Li, T. Sun, Z. Xie et al., Nanoscale aggregates of porphyrins: red-shifted absorption, enhanced absorbance and phototherapeutic activity. Mater. Chem. Front. 5(24), 8333–8340 (2021)

    Article  CAS  Google Scholar 

  110. J. Ling, S.D. Weitman, M.A. Miller, R.V. Moore, A.C. Bovik, Direct Raman imaging techniques for study of the subcellular distribution of a drug. Appl. Opt. 41(28), 6006–6017 (2002)

    Article  CAS  Google Scholar 

  111. V.H.S. Araujo, P.B. da Silva, I.O. Szlachetka, S.W. da Silva, B. Fonseca-Santos, M. Chorilli et al., The influence of NLC composition on curcumin loading under a physicochemical perspective and in vitro evaluation. Colloids Surf. A 602, 125070 (2020)

    Article  CAS  Google Scholar 

  112. M.C. Rodrigues, L.G. Vieira, F.H. Horst, E.C. de Araújo, R. Ganassin, C. Merker et al., Photodynamic therapy mediated by aluminium-phthalocyanine nanoemulsion eliminates primary tumors and pulmonary metastases in a murine 4T1 breast adenocarcinoma model. J. Photochem. Photobiol., B 204, 111808 (2020)

    Article  CAS  Google Scholar 

  113. V.P. Grover, J.M. Tognarelli, M.M. Crossey, I.J. Cox, S.D. Taylor-Robinson, M.J. McPhail, Magnetic resonance imaging: principles and techniques: lessons for clinicians. J. Clin. Exp. Hepatol. 5(3), 246–255 (2015)

    Article  Google Scholar 

  114. V. Paefgen, D. Doleschel, F. Kiessling, Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery. Front. Pharmacol. 6, 197 (2015)

    Article  CAS  Google Scholar 

  115. P.S. Sheeran, S. Luois, P.A. Dayton, T.O. Matsunaga, Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. Langmuir 27(17), 10412–10420 (2011)

    Article  CAS  Google Scholar 

  116. D.A. Fernandes, M.C. Kolios, Intrinsically absorbing photoacoustic and ultrasound contrast agents for cancer therapy and imaging. Nanotechnology 29(50), 505103 (2018)

    Article  CAS  Google Scholar 

  117. Q. Chen, J. Yu, K. Kim, optically-triggered phase-transition droplets for photoacoustic imaging. Biomed. Eng. Lett. 8(2), 223–229 (2018)

    Article  Google Scholar 

  118. K.S. Caldemeyer, K.A. Buckwalter, The basic principles of computed tomography and magnetic resonance imaging. J. Am. Acad. Dermatol. 41(5), 768–771 (1999)

    Article  CAS  Google Scholar 

  119. A. Berger, How does it work? Positron emission tomography. BMJ 326(7404):1449 (2003). https://doi.org/10.1136/bmj.326.7404.1449.

  120. W. Strober, Trypan blue exclusion test of cell viability. Curr. Protoc. Immunol. 21(1), A.3B.1–A.3B.2 (1997).

  121. K. Präbst, H. Engelhardt, S. Ringgeler, H. Hübner, Basic colorimetric proliferation assays: MTT, WST, and resazurin. Cell Viability Assays 1–17 (2017).

  122. T.L. Riss, R.A. Moravec, A.L. Niles, S. Duellman, H.A. Benink, T.J. Worzella, et al., Cell viability assays. Assay Guidance Manual (2016).

  123. T. Decker, M.-L. Lohmann-Matthes, A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J. Immunol. Methods 115(1), 61–69 (1988)

    Article  CAS  Google Scholar 

  124. P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. Mcmahon, D. Vistica, et al., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82(13), 1107–1112 (1990).

  125. E. Borenfreund, J.A. Puerner, A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90). J. Tissue Cult. Methods 9(1), 7–9 (1985)

    Article  Google Scholar 

  126. M. Feoktistova, P. Geserick, M. Leverkus, Crystal violet assay for determining viability of cultured cells. Cold Spring Harbor Protocols 2016(4):pdb. prot087379 (2016).

  127. J. Obrien, I. Wilson, T. Orton, F. Pognan, Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur. J. Biochem. 267(17), 5421–5426 (2000)

  128. A. Schreer, C. Tinson, J.P. Sherry, K. Schirmer, Application of Alamar blue/5-carboxyfluorescein diacetate acetoxymethyl ester as a noninvasive cell viability assay in primary hepatocytes from rainbow trout. Anal. Biochem. 344(1), 76–85 (2005)

    Article  CAS  Google Scholar 

  129. A.L. Niles, R.A. Moravec, T.L. Riss, In vitro viability and cytotoxicity testing and same-well multi-parametric combinations for high throughput screening. Curr. Chem. Genomics 3, 33 (2009)

    Article  CAS  Google Scholar 

  130. P.E. Andreotti, I.A. Cree, C.M. Kurbacher, D.M. Hartmann, D. Linder, G. Harel et al., Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Can. Res. 55(22), 5276–5282 (1995)

    CAS  Google Scholar 

  131. S.J. Duellman, W. Zhou, P. Meisenheimer, G. Vidugiris, J.J. Cali, P. Gautam et al., Bioluminescent, nonlytic, real-time cell viability assay and use in inhibitor screening. Assay Drug Dev. Technol. 13(8), 456–465 (2015)

    Article  CAS  Google Scholar 

  132. G. Ahmad, G.G. Mackenzie, J. Egan, M.M. Amiji, DHA-SBT-1214 taxoid nanoemulsion and anti–PD-L1 antibody combination therapy enhances antitumor efficacy in a syngeneic pancreatic adenocarcinoma model. Mol. Cancer Ther. 18(11), 1961–1972 (2019)

    Article  CAS  Google Scholar 

  133. M.H. Oh, J.S. Kim, J.Y. Lee, T.G. Park, Y.S. Nam, Radio-opaque theranostic nanoemulsions with synergistic anti-cancer activity of paclitaxel and Bcl-2 siRNA. RSC Adv. 3(34), 14642–14651 (2013)

    Article  CAS  Google Scholar 

  134. Y. Zhang, S. Bo, T. Feng, X. Qin, Y. Wan, S. Jiang et al., A versatile theranostic Nanoemulsion for architecture-dependent multimodal imaging and dually augmented photodynamic therapy. Adv. Mater. 31(21), 1806444 (2019)

    Article  CAS  Google Scholar 

  135. M. Kurpiers, J.D. Wolf, C. Steinbring, S. Zaichik, A. Bernkop-Schnürch, Zeta potential changing nanoemulsions based on phosphate moiety cleavage of a PEGylated surfactant. J. Mol. Liq. 316, 113868 (2020)

    Article  CAS  Google Scholar 

  136. G. Chen, K. Wang, P. Wu, Y. Wang, Z. Zhou, L. Yin et al., Development of fluorinated polyplex nanoemulsions for improved small interfering RNA delivery and cancer therapy. Nano Res. 11(7), 3746–3761 (2018)

    Article  CAS  Google Scholar 

  137. M.P. Le Jia, M. Fan, X. Tan, Y. Wang, M. Huang, Y. Liu et al., A pH-responsive pickering nanoemulsion for specified spatial delivery of immune checkpoint inhibitor and chemotherapy agent to tumors. Theranostics. 10(22), 9956 (2020)

    Article  CAS  Google Scholar 

  138. A. Gianella, P.A. Jarzyna, V. Mani, S. Ramachandran, C. Calcagno, J. Tang et al., Multifunctional nanoemulsion platform for imaging guided therapy evaluated in experimental cancer. ACS Nano 5(6), 4422–4433 (2011)

    Article  CAS  Google Scholar 

  139. N. Bertrand, J. Wu, X. Xu, N. Kamaly, O.C. Farokhzad, Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Deliv. Rev. 66, 2–25 (2014)

    Article  CAS  Google Scholar 

  140. S. Behzadi, V. Serpooshan, W. Tao, M.A. Hamaly, M.Y. Alkawareek, E.C. Dreaden et al., Cellular uptake of nanoparticles: journey inside the cell. Chem. Soc. Rev. 46(14), 4218–4244 (2017)

    Article  CAS  Google Scholar 

  141. Y. Zhang, M. Yang, N.G. Portney, D. Cui, G. Budak, E. Ozbay et al., Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed. Microdevice 10(2), 321–328 (2008)

    Article  CAS  Google Scholar 

  142. W. Le, Z. Cui, Natural cancer-killing activity of human granulocytes. Integr. Cancer Sci. Ther. 5 (2018)

  143. S.M. Narum, T. Le, D.P. Le, J.C. Lee, N.D. Donahue, W. Yang, et al., Passive targeting in nanomedicine: fundamental concepts, body interactions, and clinical potential, in Nanoparticles for Biomedical Applications (Elsevier, New York, 2020) pp. 37–53.

  144. D. Gadhave, B. Gorain, A. Tagalpallewar, C. Kokare, Intranasal teriflunomide microemulsion: An improved chemotherapeutic approach in glioblastoma. Journal of Drug Delivery Science and Technology. 51, 276–289 (2019)

    Article  CAS  Google Scholar 

  145. Y.-G. Wang, H. Kim, S. Mun, D. Kim, Y. Choi, Indocyanine green-loaded perfluorocarbon nanoemulsions for bimodal 19F-magnetic resonance/nearinfrared fluorescence imaging and subsequent phototherapy. Quant. Imaging Med. Surg. 3(3), 132 (2013)

    Google Scholar 

  146. A.R. Barres, M.R. Wimmer, S. Mecozzi, Multicompartment theranostic nanoemulsions stabilized by a triphilic semifluorinated block copolymer. Mol. Pharm. 14(11), 3916–3926 (2017)

    Article  CAS  Google Scholar 

  147. K. Loskutova, D. Grishenkov, M. Ghorbani, Review on acoustic droplet vaporization in ultrasound diagnostics and therapeutics. BioMed research international (2019).

  148. O.D. Kripfgans, J.B. Fowlkes, D.L. Miller, O.P. Eldevik, P.L. Carson, Acoustic droplet vaporization for therapeutic and diagnostic applications. Ultrasound Med. Biol. 26(7), 1177–1189 (2000)

    Article  CAS  Google Scholar 

  149. N. Rapoport, Z. Gao, A. Kennedy, Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. J. Natl Cancer Inst. 99(14), 1095–1106 (2007)

    Article  CAS  Google Scholar 

  150. P. Mohan, N. Rapoport, Doxorubicin as a molecular nanotheranostic agent: effect of doxorubicin encapsulation in micelles or nanoemulsions on the ultrasound-mediated intracellular delivery and nuclear trafficking. Mol. Pharm. 7(6), 1959–1973 (2010)

    Article  CAS  Google Scholar 

  151. D.A. Fernandes, M.C. Kolios, Perfluorocarbon bubbles as photoacoustic signal amplifiers for cancer theranostics. Opt. Mater. Express 9(12), 4532–4544 (2019)

    Article  CAS  Google Scholar 

  152. D.A. Fernandes, S. Appak-Baskoy, E. Berndl, M.C. Kolios, Laser activatable perfluorocarbon bubbles for imaging and therapy through enhanced absorption from coupled silica coated gold nanoparticles. RSC Adv. 11(9), 4906–4920 (2021)

    Article  CAS  Google Scholar 

  153. S. Roberts, C. Andreou, C. Choi, P. Donabedian, M. Jayaraman, E.C. Pratt et al., Sonophore-enhanced nanoemulsions for optoacoustic imaging of cancer. Chem. Sci. 9(25), 5646–5657 (2018)

    Article  CAS  Google Scholar 

  154. M. Ciocci, E. Iorio, F. Carotenuto, H.A. Khashoggi, F. Nanni, S. Melino, H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair. Oncotarget 7(51), 84338 (2016)

    Article  Google Scholar 

  155. S. Muzammil Afzal, V.M. Naidu, N. Harishankar, V. Kishan, Albumin anchored docetaxel lipid nanoemulsion for improved targeting efficiency–preparation, characterization, cytotoxic, antitumor and in vivo imaging studies. Drug Delivery 23(4), 1355–1363 (2016)

    Article  CAS  Google Scholar 

  156. A. Loureiro, E. Nogueira, N.G. Azoia, M.P. Sárria, A.S. Abreu, U. Shimanovich et al., Size controlled protein nanoemulsions for active targeting of folate receptor positive cells. Colloids Surf. B 135, 90–98 (2015)

    Article  CAS  Google Scholar 

  157. S. Ganta, A. Singh, Y. Rawal, J. Cacaccio, N.R. Patel, P. Kulkarni et al., Formulation development of a novel targeted theranostic nanoemulsion of docetaxel to overcome multidrug resistance in ovarian cancer. Drug Delivery 23(3), 958–970 (2016)

    Article  CAS  Google Scholar 

  158. N.R. Patel, A. Piroyan, A.H. Nack, C.A. Galati, M. McHugh, S. Orosz et al., Design, synthesis, and characterization of folate-targeted platinum-loaded theranostic nanoemulsions for therapy and imaging of ovarian cancer. Mol. Pharm. 13(6), 1996–2009 (2016)

    Article  CAS  Google Scholar 

  159. M. Nikanjam, A.R. Gibbs, C.A. Hunt, T.F. Budinger, T.M. Forte, Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme. J. Control. Release 124(3), 163–171 (2007)

    Article  CAS  Google Scholar 

  160. P.K. Bae, B.H. Chung, Multiplexed detection of various breast cancer cells by perfluorocarbon/quantum dot nanoemulsions conjugated with antibodies. Nano Convergence. 1(1), 1–8 (2014)

    Article  CAS  Google Scholar 

  161. L. Deng, X. Cai, D. Sheng, Y. Yang, E.M. Strohm, Z. Wang et al., A laser-activated biocompatible theranostic nanoagent for targeted multimodal imaging and photothermal therapy. Theranostics. 7(18), 4410 (2017)

    Article  CAS  Google Scholar 

  162. G. Iaccarino, M. Profeta, R. Vecchione, P.A. Netti, Matrix metalloproteinase-cleavable nanocapsules for tumor-activated drug release. Acta Biomater. 89, 265–278 (2019)

    Article  CAS  Google Scholar 

  163. C. Prasad, E. Bhatia, R. Banerjee, Curcumin encapsulated lecithin nanoemulsions: an oral platform for ultrasound mediated spatiotemporal delivery of curcumin to the tumor. Sci. Rep. 10(1), 1–15 (2020)

    Article  CAS  Google Scholar 

  164. W. Fan, Z. Yu, H. Peng, H. He, Y. Lu, J. Qi et al., Effect of particle size on the pharmacokinetics and biodistribution of parenteral nanoemulsions. Int. J. Pharm. 586, 119551 (2020)

    Article  CAS  Google Scholar 

Download references

Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Toronto, Canada

    Donald A. Fernandes

Authors
  1. Donald A. Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Donald Fernandes contributed and was involved in all aspects of the work.

Corresponding author

Correspondence to Donald A. Fernandes.

Ethics declarations

Conflict of interest

The author has no relevant financial or non-financial interests to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernandes, D.A. Review on the applications of nanoemulsions in cancer theranostics. Journal of Materials Research 37, 1953–1977 (2022). https://doi.org/10.1557/s43578-022-00583-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/s43578-022-00583-5

Keywords

Search

Navigation