Skip to main content
SpringerLink
Log in

Nanoscale chemical imaging of individual chemotherapeutic cytarabine-loaded liposomal nanocarriers

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Dosage of chemotherapeutic drugs is a tradeoff between efficacy and side-effects. Liposomes are nanocarriers that increase therapy efficacy and minimize side-effects by delivering otherwise difficult to administer therapeutics with improved efficiency and selectivity. Still, variabilities in liposome preparation require assessing drug encapsulation efficiency at the single liposome level, an information that, for non-fluorescent therapeutic cargos, is inaccessible due to the minute drug load per liposome. Photothermal induced resonance (PTIR) provides nanoscale compositional specificity, up to now, by leveraging an atomic force microscope (AFM) tip contacting the sample to transduce the sample’s photothermal expansion. However, on soft samples (e.g., liposomes) PTIR effectiveness is reduced due to the likelihood of tip-induced sample damage and inefficient AFM transduction. Here, individual liposomes loaded with the chemotherapeutic drug cytarabine are deposited intact from suspension via nano-electrospray gas-phase electrophoretic mobility molecular analysis (nES-GEMMA) collection and characterized at the nanoscale with the chemically-sensitive PTIR method. A new tapping-mode PTIR imaging paradigm based on heterodyne detection is shown to be better adapted to measure soft samples, yielding cytarabine distribution in individual liposomes and enabling classification of empty and drug-loaded liposomes. The measurements highlight PTIR capability to detect ∼ 103 cytarabine molecules (∼ 1.7 zmol) label-free and non-destructively.

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

Similar content being viewed by others

References

  1. Boisselier, E.; Astruc, D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 2009, 38, 1759–1782.

    Article  Google Scholar 

  2. Ding, J.; Liang, T.; Zhou, Y.; He, Z.; Min, Q.; Jiang, L.; Zhu, J. Hyaluronidase-triggered anticancer drug and siRNA delivery from cascaded targeting nanoparticles for drug-resistant breast cancer therapy. Nano Res. 2017, 10, 690–703.

    Article  Google Scholar 

  3. Von Maltzahn, G.; Park, J. H.; Lin, K. Y.; Singh, N.; Schwöppe, C.; Mesters, R.; Berdel, W. E.; Ruoslahti, E.; Sailor, M. J.; Bhatia, S. N. Nanoparticles that communicate in vivo to amplify tumour targeting. Nat. Mater. 2011, 10, 545–552.

    Article  Google Scholar 

  4. Lee, D. E.; Koo, H.; Sun, I. C.; Ryu, J. H.; Kim, K.; Kwon, I. C. Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem. Soc. Rev. 2012, 41, 2656–2672.

    Article  Google Scholar 

  5. Thakor, A. S.; Gambhir, S. S. Nanooncology: The future of cancer diagnosis and therapy. CA: A Cancer J. Clin. 2013, 63, 395–418.

    Google Scholar 

  6. Senapati, S.; Mahanta, A. K.; Kumar, S.; Maiti, P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct. Target. Ther. 2018, 3, 7.

    Article  Google Scholar 

  7. Lammers, T.; Hennink, W. E.; Storm, G. Tumour-targeted nanomedicines: Principles and practice. Br. J. Cancer 2008, 99, 392–397.

    Article  Google Scholar 

  8. Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751–760.

    Article  Google Scholar 

  9. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005, 4, 145–160.

    Article  Google Scholar 

  10. Morton, S. W.; Lee, M. J.; Deng, Z. J.; Dreaden, E. C.; Siouve, E.; Shopsowitz, K. E.; Shah, N. J.; Yaffe, M. B.; Hammond, P. T. A nanoparticle-based combination chemotherapy delivery system for enhanced tumor killing by dynamic rewiring of signaling pathways. Sci. Signal. 2014, 7, ra44.

    Article  Google Scholar 

  11. Zhang, Y.; Chan, H. F.; Leong, K. W. Advanced materials and processing for drug delivery: The past and the future. Adv. Drug Deliv. Rev. 2013, 65, 104–120.

    Article  Google Scholar 

  12. Venditto, V. J.; Szoka Jr, F. C. Cancer nanomedicines: So many papers and so few drugs! Adv. Drug Deliv. Rev. 2013, 65, 80–88.

    Article  Google Scholar 

  13. Allen, T. M.; Cullis, P. R. Liposomal drug delivery systems: From concept to clinical applications. Adv. Drug Deliv. Rev. 2013, 65, 36–48.

    Article  Google Scholar 

  14. Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S. Y.; Sood, A. K.; Hua, S. S. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 2015, 6, 286.

    Article  Google Scholar 

  15. Young, S. A.; Smith, T. K. Lipids and liposomes in the enhancement of health and treatment of disease. In Drug Discovery and Development - From Molecules to Medicine. Vallisuta, O.; Olimat, S., Eds.; InTech: Croatia, 2015; pp 133–162.

    Google Scholar 

  16. Bozzuto, G.; Molinari, A. Liposomes as nanomedical devices. Int. J. Nanomedicine 2015, 10, 975–999.

    Article  Google Scholar 

  17. de Araújo Lopes, S. C.; dos Santos Giuberti, C.; Rocha, T. G. R.; dos Santos Ferreira, D.; Leite, E. A.; Oliveira, M. C. Liposomes as carriers of anticancer drugs. In Cancer Treatment - Conventional and Innovative Approaches. Rangel, L., Ed.; InTech: Rijeka, 2013; pp 85–124.

    Google Scholar 

  18. Çagdas, M.; Sezer, A. D.; Bucak, S. Liposomes as potential drug carrier systems for drug delivery. In Application of Nanotechnology in Drug Delivery. Sezer, A. D., ed.; InTech: Rijeka, 2014; pp 1–50.

    Google Scholar 

  19. Schwendener, R. A. Liposomes as vaccine delivery systems: A review of the recent advances. Ther. Adv. Vaccines 2014, 2, 159–182.

    Article  Google Scholar 

  20. Rasoulianboroujeni, M.; Kupgan, G.; Moghadam, F.; Tahriri, M.; Boughdachi, A.; Khoshkenar, P.; Ambrose, J. J.; Kiaie, N.; Vashaee, D.; Ramsey, J. D. et al. Development of a DNA-liposome complex for gene delivery applications. Mater. Sci. Eng. C 2017, 75, 191–197.

    Article  Google Scholar 

  21. Saffari, M.; Moghimi, H. R.; Dass, C. R. Barriers to liposomal gene delivery: From application site to the target. Iran. J. Pharm. Res. 2016, 15, 3–17.

    Google Scholar 

  22. Bulbake, U.; Doppalapudi, S.; Kommineni, N.; Khan, W. Liposomal formulations in clinical use: An updated review. Pharmaceutics 2017, 9, 12.

    Article  Google Scholar 

  23. Pillai, G. Nanomedicines for cancer therapy: An update of fda approved and those under various stages of development. Pharm. Pharm. Sci. 2014, 1, 13.

    Google Scholar 

  24. El-Subbagh, H. I.; Al-Badr, A. A. Cytarabine. In Profiles of Drug Substances, Excipients, and Related Methodology. Brittain, H. G., ed.; Elsevier: Amsterdam, 2009; pp 37–113.

    Google Scholar 

  25. Germain, M.; Meyre, M. E.; Poul, L.; Paolini, M.; Berjaud, C.; Mpambani, F.; Bergere, M.; Levy, L.; Pottier, A. Priming the body to receive the therapeutic agent to redefine treatment benefit/risk profile. Sci. Rep. 2018, 8, 4797.

    Article  Google Scholar 

  26. Park, B. H.; von Maltzahn, G.; Ong, L. L.; Centrone, A.; Hatton, T. A.; Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J. Cooperative nanoparticles for tumor detection and photothermally triggered drug delivery. Adv. Mater. 2010, 22, 880–885.

    Article  Google Scholar 

  27. Mullen, D. G.; Holl, M. M. B. Heterogeneous ligand–nanoparticle distributions: A major obstacle to scientific understanding and commercial translation. ACC. Chem. Res. 2011, 44, 1135–1145.

    Article  Google Scholar 

  28. Lohse, B.; Bolinger, P. Y.; Stamou, D. Encapsulation efficiency measured on single small unilamellar vesicles. J. Am. Chem. Soc. 2008, 130, 14372–14373.

    Article  Google Scholar 

  29. Ernsting, M. J.; Murakami, M.; Roy, A.; Li, S. D. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J. Control. Release 2013, 172, 782–794.

    Article  Google Scholar 

  30. Ohnishi, N.; Yamamoto, E.; Tomida, H.; Hyodo, K.; Ishihara, H.; Kikuchi, H.; Tahara, K.; Takeuchi, H. Rapid determination of the encapsulation efficiency of a liposome formulation using column-switching HPLC. Int. J. Pharm. 2013, 441, 67–74.

    Article  Google Scholar 

  31. Zhang, X. M.; Patel, A. B.; de Graaf, R. A.; Behar, K. L. Determination of liposomal encapsulation efficiency using proton NMR spectroscopy. Chem. Phys. Lipids 2004, 127, 113–120.

    Article  Google Scholar 

  32. Franzen, U.; Nguyen, T. T. T. N.; Vermehren, C.; Gammelgaard, B.; Østergaard, J. Characterization of a liposome-based formulation of oxaliplatin using capillary electrophoresis: Encapsulation and leakage. J. Pharm. Biomed. Anal. 2011, 55, 16–22.

    Article  Google Scholar 

  33. Chen, C. X.; Zhu, S. B.; Wang, S.; Zhang, W. Q.; Cheng, Y.; Yan, X. M. Multiparameter quantification of liposomal nanomedicines at the singleparticle level by high-sensitivity flow cytometry. ACS Appl. Mater. Interfaces 2017, 9, 13913–13919.

    Article  Google Scholar 

  34. Jesorka, A.; Orwar, O. Liposomes: Technologies and analytical applications. Annu. Rev. Anal. Chem. 2008, 1, 801–832.

    Article  Google Scholar 

  35. Weiss, V. U.; Urey, C.; Gondikas, A.; Golesne, M.; Friedbacher, G.; von der Kammer, F.; Hofmann, T.; Andersson, R.; Marko-Varga, G.; Marchetti-Deschmann, M. et al. Nano electrospray gas-phase electrophoretic mobility molecular analysis (nES-GEMMA) of liposomes: Applicability of the technique for nano vesicle batch control. Analyst 2016, 141, 6042–6050.

    Article  Google Scholar 

  36. Urey, C.; Weiss, V. U.; Gondikas, A.; von der Kammer, F.; Hofmann, T.; Marchetti-Deschmann, M.; Allmaier, G.; Marko-Varga, G.; Andersson, R. Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles. Int. J. Pharm. 2016, 513, 309–318.

    Article  Google Scholar 

  37. Weiss, V. U.; Lehner, A.; Kerul, L.; Grombe, R.; Kratzmeier, M.; Marchetti-Deschmann, M.; Allmaier, G. Characterization of cross-linked gelatin nanoparticles by electrophoretic techniques in the liquid and the gas phase. Electrophoresis 2013, 34, 3267–3276.

    Article  Google Scholar 

  38. Kaufman, S. L.; Skogen, J. W.; Dorman, F. D.; Zarrin, F. Macromolecule analysis based on electrophoretic mobility in air: Globular proteins. Anal. Chem. 1996, 68, 1895–1904.

    Article  Google Scholar 

  39. Tycova, A.; Prikryl, J.; Foret, F. Reproducible preparation of nanospray tips for capillary electrophoresis coupled to mass spectrometry using 3D printed grinding device. Electrophoresis 2016, 37, 924–930.

    Article  Google Scholar 

  40. Bangham, A. D.; Standish, M. M.; Watkins, J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 1965, 13, 238–252.

    Article  Google Scholar 

  41. Kinney, P. D.; Pui, D. Y. H.; Mulliolland, G. W.; Bryner, N. P. Use of the electrostatic classification method to size 0.1 µm SRM particles—a feasibility study. J. Res. Natl. Inst. Stand. Technol. 1991, 96, 147–176.

    Article  Google Scholar 

  42. Lewis, R. N.; McElhaney, R. N.; Pohle, W.; Mantsch, H. H. Components of the carbonyl stretching band in the infrared spectra of hydrated 1,2-diacylglycerolipid bilayers: A reevaluation. Biophys. J. 1994, 67, 2367–2375.

    Article  Google Scholar 

  43. Socrates, G. Infrared and Raman Characteristic Group Frequencies: Tables and Charts; 3rd ed. John Wiley and Sons: Chichester, 2001.

    Google Scholar 

  44. Centrone, A. Infrared imaging and spectroscopy beyond the diffraction limit. Annu. Rev. Anal. Chem. 2015, 8, 101–126.

    Article  Google Scholar 

  45. Dazzi, A.; Prater, C. B. AFM-IR: Technology and applications in nanoscale infrared spectroscopy and chemical imaging. Chem. Rev. 2017, 117, 5146–5173.

    Article  Google Scholar 

  46. Dazzi, A.; Glotin, F.; Carminati, R. Theory of infrared nanospectroscopy by photothermal induced resonance. J. Appl. Phys. 2010, 107, 124519.

    Article  Google Scholar 

  47. Lahiri, B.; Holland, G.; Centrone, A. Chemical imaging beyond the diffraction limit: Experimental validation of the PTIR technique. Small 2013, 9, 439–445.

    Article  Google Scholar 

  48. Katzenmeyer, A. M.; Holland, G.; Kjoller, K.; Centrone, A. Absorption spectroscopy and imaging from the visible through mid-infrared with 20 nm resolution. Anal. Chem. 2015, 87, 3154–3159.

    Article  Google Scholar 

  49. Lu, F.; Jin, M. Z.; Belkin, M. A. Tip-enhanced infrared nanospectroscopy via molecular expansion force detection. Nat. Photonics 2014, 8, 307–312.

    Article  Google Scholar 

  50. Strelcov, E.; Dong, Q. F.; Li, T.; Chae, J.; Shao, Y. C.; Deng, Y. H.; Gruverman, A.; Huang, J. S.; Centrone, A. CH3NH3PbI3 perovskites: Ferroelasticity revealed. Sci. Adv. 2017, 3, e1602165.

    Article  Google Scholar 

  51. Chae, J.; Dong, Q. F.; Huang, J. S.; Centrone, A. Chloride incorporation process in CH3NH3PBI3-xClx perovskites via nanoscale bandgap maps. Nano Lett. 2015, 15, 8114–8121.

    Article  Google Scholar 

  52. Dong, R.; Fang, Y. J.; Chae, J.; Dai, J.; Xiao, Z. G.; Dong, Q. F.; Yuan, Y. B.; Centrone, A.; Zeng, X. C.; Huang, J. High-gain and low-driving-voltage photodetectors based on organolead triiodide perovskites. Adv. Mater. 2015, 27, 1912–1918.

    Article  Google Scholar 

  53. van Eerdenbrugh, B.; Lo, M.; Kjoller, K.; Marcott, C.; Taylor, L. S. Nanoscale mid-infrared imaging of phase separation in a drug–polymer blend. J. Pharm. Sci. 2012, 101, 2066–2073.

    Article  Google Scholar 

  54. Morsch, S.; van Driel, B. A.; van den Berg, K. J.; Dik, J. Investigating the photocatalytic degradation of oil paint using ATR-IR and AFM-IR. Appl. Mater. Interfaces 2017, 9, 10169–10179.

    Article  Google Scholar 

  55. Ghosh, S.; Kouamé, N. A.; Ramos, L.; Remita, S.; Dazzi, A.; Deniset-Besseau, A.; Beaunier, P.; Goubard, F.; Aubert, P. H.; Remita, H. Conducting polymer nanostructures for photocatalysis under visible light. Nat. Mater. 2015, 14, 505–511.

    Article  Google Scholar 

  56. Tri, P. N.; Prud’homme, R. E. Nanoscale lamellar assembly and segregation mechanism of poly (3-hydroxybutyrate)/poly(ethylene glycol) blends. Macromolecules 2018, 51, 181–188.

    Article  Google Scholar 

  57. Morsch, S.; Liu, Y. W.; Lyon, S. B.; Gibbon, S. R. Insights into epoxy network nanostructural heterogeneity using AFM-IR. Appl. Mater. Interfaces 2016, 8, 959–966.

    Article  Google Scholar 

  58. Chae, J.; Lahiri, B.; Centrone, A. Engineering near-field SEIRA enhancements in plasmonic resonators. ACS Photonics 2016, 3, 87–95.

    Article  Google Scholar 

  59. Lahiri, B.; Holland, G.; Aksyuk, V.; Centrone, A. Nanoscale imaging of plasmonic hot spots and dark modes with the photothermal-induced resonance technique. Nano Lett. 2013, 13, 3218–3224.

    Article  Google Scholar 

  60. Katzenmeyer, A. M.; Chae, J.; Kasica, R.; Holland, G.; Lahiri, B.; Centrone, A. Nanoscale imaging and spectroscopy of plasmonic modes with the PTIR technique. Adv. Opt. Mater. 2014, 2, 718–722.

    Article  Google Scholar 

  61. Katzenmeyer, A. M.; Canivet, J.; Holland, G.; Farrusseng, D.; Centrone, A. Assessing chemical heterogeneity at the nanoscale in mixed-ligand metal-organic frameworks with the PTIR technique. Angew. Chem., Int. Ed. 2014, 53, 2852–2856.

    Article  Google Scholar 

  62. Brown, L. V; Davanco, M.; Sun, Z. Y.; Kretinin, A.; Chen, Y. G.; Matson, J. R.; Vurgaftman, I.; Sharac, N.; Giles, A. J.; Fogler, M. M. et al. Nanoscale mapping and spectroscopy of nonradiative hyperbolic modes in hexagonal boron nitride nanostructures. Nano Lett. 2018, 18, 1628–1636.

    Article  Google Scholar 

  63. Rosenberger, M. R.; Wang, M. C.; Xie, X.; Rogers, J. A.; Nam, S.; King, W. P. Measuring individual carbon nanotubes and single graphene sheets using atomic force microscope infrared spectroscopy. Nanotechnology 2017, 28, 355707.

    Article  Google Scholar 

  64. Ramer, G.; Balbekova, A.; Schwaighofer, A.; Lendl, B. Method for time-resolved monitoring of a solid state biological film using photothermal infrared nanoscopy on the example of poly-L-lysine. Anal. Chem. 2015, 87, 4415–4420.

    Article  Google Scholar 

  65. Ruggeri, F. S.; Habchi, J.; Cerreta, A.; Dietler, G. AFM-based single molecule techniques: Unraveling the amyloid pathogenic species. Curr. Pharm. Des. 2016, 22, 3950–3970.

    Article  Google Scholar 

  66. Dazzi, A.; Prater, C. B.; Hu, Q. C.; Chase, D. B.; Rabolt, J. F.; Marcott, C. AFM–IR: Combining atomic force microscopy and infrared spectroscopy for nanoscale chemical characterization. Appl. Spectrosc. 2012, 66, 1365–1384.

    Article  Google Scholar 

  67. Marcott, C.; Lo, M.; Kjoller, K.; Fiat, F.; Baghdadli, N.; Balooch, G.; Luengo, G. S. Localization of human hair structural lipids using nanoscale infrared spectroscopy and imaging. Appl. Spectrosc. 2014, 68, 564–569.

    Article  Google Scholar 

  68. Yarrow, F.; Kennedy, E.; Salaun, F.; Rice, J. H. Sub-wavelength infrared imaging of lipids. Biomed. Opt. Express, 2011, 2, 37–43.

    Article  Google Scholar 

  69. Pancani, E.; Mathurin, J.; Bilent, S.; Bernet-Camard, M. F.; Dazzi, A.; Deniset-Besseau, A.; Gref, R. High-resolution label-free detection of biocompatible polymeric nanoparticles in cells. Part. Part. Syst. Charact. 2018, 35, 1700457.

    Article  Google Scholar 

  70. Kang, M.; Tuteja, M.; Centrone, A.; Topgaard, D.; Leal, C. Nanostructured lipid-based films for substrate-mediated applications in biotechnology. Adv. Funct. Mater. 2018, 28, 1704356.

    Article  Google Scholar 

  71. Tuteja, M.; Kang, M.; Leal, C.; Centrone, A. Nanoscale partitioning of paclitaxel in hybrid lipid–polymer membranes. Analyst 2018, 143, 3808–3813.

    Article  Google Scholar 

  72. Ramer, G.; Ruggeri, F. S.; Levin, A.; Knowles, T. P. J.; Centrone, A. Determination of polypeptide conformation with nanoscale resolution in water. ACS Nano 2018, 12, 6612–6619.

    Article  Google Scholar 

  73. Jin, M. Z.; Lu, F.; Belkin, M. A. High-sensitivity infrared vibrational nanospectroscopy in water. Light Sci. Appl. 2017, 6, e17096.

    Article  Google Scholar 

  74. Xiao, L. F.; Schultz, Z. D. Spectroscopic imaging at the nanoscale: Technologies and recent applications. Anal. Chem. 2018, 90, 440–458.

    Article  Google Scholar 

  75. Mayet, C.; Dazzi, A.; Prazeres, R.; Allot, F.; Glotin, F.; Ortega, J. M. Sub-100 nm IR spectromicroscopy of living cells. Opt. Lett. 2008, 33, 1611–1613.

    Article  Google Scholar 

  76. Dazzi, A.; Prazeres, R.; Glotin, F.; Ortega, J. M.; Al-Sawaftah, M.; de Frutos, M. Chemical mapping of the distribution of viruses into infected bacteria with a photothermal method. Ultramicroscopy 2008, 108, 635–641.

    Article  Google Scholar 

  77. Ramer, G.; Aksyuk, V. A.; Centrone, A. Quantitative chemical analysis at the nanoscale using the photothermal induced resonance technique. Anal. Chem. 2017, 89, 13524–13531.

    Article  Google Scholar 

  78. Katzenmeyer, A. M.; Holland, G.; Chae, J.; Band, A.; Kjoller, K.; Centrone, A. Mid-infrared spectroscopy beyond the diffraction limit via direct measurement of the photothermal effect. Nanoscale 2015, 7, 17637–17641.

    Article  Google Scholar 

  79. Barlow, D. E.; Biffinger, J. C.; Cockrell-Zugell, A. L.; Lo, M.; Kjoller, K.; Cook, D.; Lee, K. W.; Pehrsson, P. E.; Crookes-Goodson, W. J.; Hung, C. S. et al. The importance of correcting for variable probe–sample interactions in AFM-IR spectroscopy: AFM-IR of dried bacteria on a polyurethane film. Analyst 2016, 141, 4848–4854.

    Article  Google Scholar 

  80. Rabe, U.; Janser, K.; Arnold, W. Vibrations of free and surface-coupled atomic force microscope cantilevers: Theory and experiment. Rev. Sci. Instrum. 1996, 67, 3281–3293.

    Article  Google Scholar 

  81. Ramer, G.; Reisenbauer, F.; Steindl, B.; Tomischko, W.; Lendl, B. Implementation of resonance tracking for assuring reliability in resonance enhanced photothermal infrared spectroscopy and imaging. Appl. Spectrosc. 2017, 71, 2013–2020.

    Article  Google Scholar 

  82. Hu, S. M. Infrared absorption spectra of SiO2 precipitates of various shapes in silicon: Calculated and experimental. J. Appl. Phys. 1980, 51, 5945–5948.

    Article  Google Scholar 

  83. Last, J. A.; Russell, P.; Nealey, P. F.; Murphy, C. J. The applications of atomic force microscopy to vision science. Invest. Ophthalmol. Vis. Sci. 2010, 51, 6083–6094.

    Article  Google Scholar 

  84. Tetard, L.; Passian, A.; Farahi, R. H.; Thundat, T.; Davison, B. H. Optonanomechanical spectroscopic material characterization. Nat. Nanotechnol. 2015, 10, 870–877.

    Article  Google Scholar 

  85. Chae, J.; An, S. M.; Ramer, G.; Stavila, V.; Holland, G.; Yoon, Y.; Talin, A. A.; Allendorf, M.; Aksyuk, V. A.; Centrone, A. Nanophotonic atomic force microscope transducers enable chemical composition and thermal conductivity measurements at the nanoscale. Nano Lett. 2017, 17, 5587–5594.

    Article  Google Scholar 

Download references

Acknowledgements

K. W., G. R. and A. C. wrote the manuscript with inputs from V. U. W., G. A. and B. L. G. A., B. L., and A. C. supervised the project. K. W. performed and evaluated contact- and tapping-mode PTIR measurements with support from G. R. and A. C. V. U. W. prepared liposomes and performed nES-GEMMA collection. All authors discussed the results and commented on the manuscript. K. W. acknowledges financial support by the Austrian Research Funding Association (FFG) within the research project “NanoSpec – High-resolution near-field infrared microscopy for the process control of nanotechnological components” (contract#843594). G. R. acknowledges support from the University of Maryland through the Cooperative Research Agreement between the University of Maryland and the National Institute of Standards and Technology Center for Nanoscale Science and Technology, Award 70NANB14H209. The authors thank Mohit Tuteja and Brian Hoskins for fruitful discussions.

Author information

Authors and Affiliations

  1. Institute of Chemical Technologies and Analytics, Research Division Environmental, Process Analytics and Sensors, TU Wien, Vienna, 1060, Austria

    Karin Wieland & Bernhard Lendl

  2. Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA

    Georg Ramer & Andrea Centrone

  3. Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, MD, 20742, USA

    Georg Ramer

  4. Institute of Chemical Technologies and Analytics, Research Division Instrumental and Imaging Analytical Chemistry, TU Wien, Vienna, 1060, Austria

    Victor U. Weiss & Guenter Allmaier

Authors
  1. Karin Wieland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georg Ramer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor U. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guenter Allmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bernhard Lendl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Centrone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Centrone.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wieland, K., Ramer, G., Weiss, V.U. et al. Nanoscale chemical imaging of individual chemotherapeutic cytarabine-loaded liposomal nanocarriers. Nano Res. 12, 197–203 (2019). https://doi.org/10.1007/s12274-018-2202-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-018-2202-x

Keywords

Search

Navigation