Four-Dimensional Monitoring of Tumour Growth by Surface Enhanced Raman Scattering

ERC Advanced Grant Project

4DbioSERS is an ERC Advanced Grant Project granted to Prof. Luis Liz-Marzán by the European Research Council under the European's Union Horizon 2020 (H2020-EU.1.1) /ERC grant agreement n° 787510. The 5 year research project started the 1st of October of 2018 and will run until the 30th of September 2023. More details.


Optical bioimaging is limited by visible light penetration depth and stability of fluorescent dyes over extended periods of time. Surface enhanced Raman scattering (SERS) offers the possibility to overcome these drawbacks, through SERS-encoded nanoparticle tags, which can be excited with near-IR light (within the biological transparency window), providing high intensity, stable, multiplexed signals. SERS can also be used to monitor relevant bioanalytes within cells and tissues, during the development of diseases, such as tumours. In 4DBIOSERS we shall combine both capabilities of SERS, to go well beyond the current state of the art, by building three-dimensional scaffolds that support tissue (tumour) growth within a controlled environment, so that not only the fate of each (SERS-labelled) cell within the tumour can be monitored in real time (thus adding a fourth dimension to SERS bioimaging), but also recording the release of tumour metabolites and other indicators of cellular activity. Although 4DBIOSERS can be applied to a variety of diseases, we shall focus on cancer, melanoma and breast cancer in particular, as these are readily accessible by optical methods. We aim at acquiring a better understanding of tumour growth and dynamics, while avoiding animal experimentation. 3D printing will be used to generate hybrid scaffolds where tumour and healthy cells will be co-incubated to simulate a more realistic environment, thus going well beyond the potential of 2D cell cultures. Each cell type will be encoded with ultra-bright SERS tags, so that real-time monitoring can be achieved by confocal SERS microscopy. Tumour development will be correlated with simultaneous detection of various cancer biomarkers, during standard conditions and upon addition of selected drugs. The scope of 4DBIOSERS is multidisciplinary, as it involves the design of high-end nanocomposites, development of 3D cell culture models and optimization of emerging SERS tomography methods.




3. J. Plou, M. Charconnet, I. García, J. Calvo, L.M. Liz-Marzán, Preventing Memory Effects in Surface-Enhanced Raman Scattering Substrates by Polymer Coating and Laser-Activated Deprotection
ACS Nano 2021, 15, 8984-8995
2. C. Sanchez-Cano, R. Alvarez-Puebla, J.M. Abendroth, T. Beck, R. Blick, Y. Cao, F. Caruso, I. Chakraborty, H. Chapman, C. Chen, B.E. Cohen, A.L.C. Conceição, D.P. Cormode, D. Cui, K.A. Dawson, G. Falkenberg, C. Fan, N. Feliu, M. Gao, E. Gargioni, C.-C. Glüer, F. Grüner, M. Hassan, Y. Hu, Y. Huang, S. Huber, N. Huse, Y. Kang, A. Khademhosseini, T. Keller, C. Körnig, N.A. Kotov, D. Koziej, X.-J. Liang, B. Liu, S. Liu, Y. Liu, Z. Liu, L.M. Liz-Marzán, X. Ma, A. Machicote, W. Maison, A. Mancuso, S. Megahed, B. Nickel, F. Otto, C. Palencia-Ramirez, S. Pascarelli, A. Pearson, O. Peñate-Medina, B. Qi, J. Rädler, J.J. Richardson, A. Rosenhahn, K. Rothkamm, M. Rübhausen, M.K. Sanyal, R.E. Schaak, H.-P. Schlemmer, M. Schmidt, O. Schmutzler, T. Schotten, F. Schulz, A.K. Sood, K.M. Spiers, T. Staufer, D. Stemer, A. Stierle, X. Sun, G. Tsakanova, T. Tschentscher, P.S. Weiss, H. Weller, F. Westermeier, M. Xu, H. Yan, Y. Zeng, Y. Zhao, Y. Zhao, D. Zhu, Y. Zhu, W.J. Parak, X-Ray-Based Techniques to Study the Nano-Bio Interface
ACS Nano 2021, 15, 3754-3807
1. E. Er, A. Sánchez-Iglesias, A. Silvestri, B. Arnaiz, L.M. Liz-Marzán, M. Prato, A. Criado, Metal nanoparticles/MoS2 SERS-Based Sandwich Immunoassay for alpha-Fetoprotein Detection
ACS Appl. Mater. Interfaces 2021, 13, 8823-8831



14. Y. Zhang, D. Jimenez de Aberasturi, M. Henriksen-Lacey, J. Langer, L.M. Liz-Marzán, Live Cell Surface-Enhanced Raman Spectroscopy Imaging of Intracellular pH: From Two Dimensions to Three Dimensions
ACS Sens. 2020, 5, 3194-3206
13. S. Rodal-Cedeira, A. Vázquez-Arias, G. Bodelón, A. Skorikov, S. Nuñez-Sánchez, A. La Porta, L. Polavarapu, S. Bals, L.M. Liz-Marzán, J. Pérez-Juste, I. Pastoriza-Santos, An Expanded Surface-Enhanced Raman Scattering Tags Library by Combinatorial Encapsulation of Reporter Molecules in Metal Nanoshells
ACS Nano 2020, 14, 14655-14664
12. A. Sánchez-Iglesias, X. Zhuo, W. Albrecht, S. Bals, L.M. Liz-Marzán, Tuning Size and Seed Position in Small Silver Nanorods
ACS Mater. Lett. 2020, 2, 1246-1250
11. J.E.L. Villa, I. García, D.Jimenez de Aberasturi, V. Pavlov, M.P.T. Sotomayor, L.M. Liz-Marzán, SERS-Based Immunoassay for Monitoring Cortisol-Related Disorders
Biosens. Bioelectron. 2020, 165, 112418. Free to read until September 10
10. L.H.G. Tizei, V. Mkhitaryan, H. Lourenço-Martins, L. Scarabelli, K. Watanabe, T. Taniguchi, M. Tencé, J.-D. Blazit, X. Li, A. Gloter, A. Zobelli, Luis M. Liz-Marzán, F.J. Garcia de Abajo, O. Stéphan, M. Kociak, Tailored Nanoscale Plasmon-Enhanced Vibrational Electron Spectroscopy
Nano Lett. 2020, 20, 2973-2979
9. C. Vila-Parrondo, C. García-Astrain, L.M. Liz-Marzán, Colloidal Systems Toward 3D Cell Culture Scaffolds
Adv. Coll. Interface Sci. 2020, 283, 102237. Free to read until October 8
8. C. García-Astrain, E. Lenzi, D. Jimenez de Aberasturi, M. Henriksen-Lacey, M. Binelli, L.M. Liz-Marzán, 3D-Printed Biocompatible Scaffolds with Built-In Nanoplasmonic Sensors
Adv. Funct. Mater. 2020, 30, 2005407
7. X. Zhuo, M. Henriksen-Lacey, D. Jimenez de Aberasturi, A. Sánchez-Iglesias, L.M. Liz-Marzán, Shielded Silver Nanorods for Bioapplications
Chem. Mater. 2020, 32, 5879-5889
6. G. González-Rubio, J. Mosquera, V. Kumar, A. Pedrazo-Tardajos, P. Llombart, D.M. Solís, I. Lobato, E.G. Noya, A. Guerrero-Martínez, J.M. Taboada, F. Obelleiro, L.G. MacDowell, S. Bals, L.M. Liz-Marzán, Micelle-Directed Chiral Seeded Growth on Anisotropic Gold Nanocrystals
Science 2020, 368, 1472-1477. See REPRINT
5. J. Mosquera, I. García, M. Henriksen-Lacey, M. Martínez-Calvo, M. Dhanjani, J.L. Mascareñas, L.M. Liz-Marzán, Reversible Control of Protein Corona Formation on Gold Nanoparticles Using Host-Guest Interactions
ACS Nano 2020, 14, 5382-5391
4. J. Plou, I. García, M. Charconnet, I. Astobiza, C. García-Astrain, C. Matricardi, A. Mihi, A. Carracedo, L.M. Liz-Marzán, Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media
Adv. Funct. Mater. 2020, 30, 1910335
3. D. Jimenez de Aberasturi, M. Henriksen-Lacey, L. Litti, J. Langer, L.M. Liz-Marzán, Using SERS Tags to Image the Three-Dimensional Structure of Complex Cell Models
Adv. Funct. Mater. 2020, 30, 1909655
2. L. Litti, J. Reguera, F.J. García de Abajo, M. Meneghetti, L.M. Liz-Marzán, Manipulating Chemistry through Nanoparticle Morphology
Nanoscale Horiz. 2020, 5, 102-108
1. J. Langer, D. Jimenez de Aberasturi, J. Aizpurua, R.A. Alvarez-Puebla, B. Auguié, J.J. Baumberg, G.C. Bazan, S.E. Bell, A. Boisen, A. Brolo, J. Choo, D. Cialla-May, V. Deckert, L. Fabris, K. Faulds, F.J. García de Abajo, R. Goodacre, D. Graham, A.J. Haes, C.L. Haynes, C. Huck, T. Itoh, M. Käll, J. Kneipp, N.A. Kotov, H. Kuang, E.C. Le Ru, H.K. Lee, J.-F. Li, X.Y. Ling, S.A. Maier, T. Mayerhöfer, M. Moskovits, K. Murakoshi, J.-M. Nam, S. Nie, Y. Ozaki, I. Pastoriza-Santos, J. Pérez-Juste, J. Popp, A. Pucci, S. Reich, B. Ren, G.C. Schatz, T. Shegai, S. Schlücker, L.-L. Tay, K.G. Thomas, Z.-Q. Tian, R.P. Van Duyne, T. Vo-Dinh, Y. Wang, K.A. Willets, C. Xu, H.X. Xu, Y. Xu, Y.S. Yamamoto, B. Zhao, L.M. Liz-Marzán, Present and Future of Surface-Enhanced Raman Scattering
ACS Nano 2020, 14, 28-117



4. M. Grzelczak, L.M. Liz-Marzán, R. Klajn, Stimuli-Responsive Self-Assembly of Nanoparticles
Chem. Soc. Rev. 2019, 48, 1342-1361
3. M. Quintanilla, C. Kuttner, J.D. Smith, A. Seifert, S.E. Skrabalak, L.M. Liz-Marzán, Heat Generation by Branched Au/Pd Nanocrystals: Influence of Morphology and Composition
Nanoscale 2019, 11, 19561-19570
2. M. Quintanilla, I. García, I. de Lázaro, R. García-Alvarez, M. Henriksen-Lacey, S. Vranic, K. Kostarelos, L.M. Liz-Marzán, Thermal Monitoring During Photothermia: Hybrid Probes for Simultaneous Plasmonic Heating and Near-Infrared Optical Nanothermometry
Theranostics 2019, 9, 7298-7312
1. E. Lenzi, D. Jimenez de Aberasturi, L.M. Liz-Marzán, SERS Tags for 3D Bioimaging and Biomarker Detection
ACS Sensors 2019, 4, 1126-1137

Project Members

Project head: Prof. Luis Liz-Marzán


  • Principal Investigator
    • Prof. Luis M. Liz-Marzán
  • Postdoctoral Research Associates
    • Dr. Malou Henriksen-Lacey
    • Dr. Isabel García
    • Dr. Dorleta Jimenez de Aberasturi
    • Dr. Clara García-Astrain
    • Dr. Xiaolu Zhuo
    • Dr. Carlos Renero
    • Dr. Beatriz Molina
    • Dr. Carlos de Albuquerque
  • PhD Students
    • Javier Plou
    • Christian Vila
    • Elisa Lenzi
    • Cristina de la Encarnación
    • Paula Vazquez
    • Uxue Aizarna
    • Pablo Valera
  • Research Assistants
    • Ana Sánchez-Iglesias
    • Judith Langer
    • Ada Herrero
  • Management
    • Dr. Cristina Díez

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