Nanomedicines and Theranostics

Nanomedicines are 1-100(0) nm-sized carrier materials designed to improve the biodistribution and the target site accumulation of systemically administered (chemo-) therapeutic drugs. By delivering drugs more specifically to pathological sites, and by preventing them from accumulating in potentially endangered healthy tissues, nanomedicines are able to improve the balance between the efficacy and the toxicity of systemic drug therapies.

Efforts in the Dept. of Nanomedicine and Theranostics, which is part of the Institute for Experimental Molecular Imaging at RWTH Aachen University, focus on the use of nanomedicine formulations for treating cancer and inflammatory disorders. In close collaboration with several universities (Utrecht, Twente, Maastricht) and companies in The Netherlands, with the Institute of Macromolecular Chemistry at the Czech Academy of Sciences in Prague, and with a number of colleagues at RWTH Aachen University, various different types of drug delivery systems are being evaluated, including e.g. liposomes, polymers and micelles. These carrier materials are loaded with chemotherapeutic agents and with corticosteroids, as well as with imaging agents. The resulting ‘theranostic’ nanomedicines, which contain both diagnostic and therapeutic properties within a single formulation, are considered to be useful for individualizing and improving treatments, enabling image-guided drug delivery to tumors, to metastases, to inflammatory lesions (e.g. arthritis, colitis, atherosclerosis, liver and kidney fibrosis), and to the brain. In addition, such theranostics concepts and constructs can be employed for non-invasive and quantitative efficacy monitoring, as well as for image-guided tissue engineering.

Projects at the Nanomedicine and Theranostics group are coordinated by Prof. Twan Lammers, and are performed in close collaboration with the other four working groups at the Institute for Experimental Molecular Imaging. Because of this, we are able to cover almost all aspects of nanomedicine and drug delivery research. These e.g. include the chemical procedures and the pharmaceutical technologies necessary to produce, load and label nanomedicines; the use of state-of-the-art in vivo and ex vivo imaging techniques; and access to advanced animal models. Moreover, efforts in our group profit from the shared intention of the institute’s PIs to deeply understand the underlying mechanisms of cancer and inflammatory disorders, related e.g. to angiogenesis, inflammation, macrophage infiltration and macrophage polarization. As somewhat smaller side projects, we also work on multi-drug resistance, on sonoporation, on nanotoxicity testing, and on theranostic tissue engineering.

Our work is supported by the German Research Foundation (DFG), by the European research Council (ERC) and by the European Commission (EC). In addition, several group members have managed to obtain own internal funding (RWTH) or individual scholarships, provided e.g. by the German Academic Exchange Service (DAAD).

Univ.- Prof.
Dr. Dr. T. Lammers

Selected publications

Research Papers

    1. Ergen C, Heymann F, Al Rawashdeh W, Gremse F, Bartneck M, Panzer U, Pola R, Pechar M, Storm G, Mohr N, Barz M, Zentel R, Kiessling F, Trautwein C, Lammers T, and Tacke F. Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles. Biomaterials. 2017;114:106‑120.

    1. Theek B, Baues M, Ojha T, Möckel D, Veettil SK, Steitz J, van Bloois L, Storm G, Kiessling F, and Lammers T. Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. J Control Release. 2016;231:77‑85.

    1. Lammers T, Koczera P, Fokong S, Gremse F, Ehling J, Vogt M, Pich A, Storm G, van Zandvoort M, and Kiessling F. Theranostic USPIO-Loaded Microbubbles for Mediating and Monitoring Blood-Brain Barrier Permeation. Adv Funct Mater. 2015;25(1):36‑43.

    1. Quan L, Zhang Y, Crielaard BJ, Dusad A, Lele SM, Rijcken CJF, Metselaar JM, Kostková H, Etrych T, Ulbrich K, Kiessling F, Mikuls TR, Hennink WE, Storm G, Lammers T, and Wang D. Nanomedicines for inflammatory arthritis: head-to-head comparison of glucocorticoid-containing polymers, micelles, and liposomes. ACS Nano. 2014;8(1):458‑66.

    1. Kunjachan S, Pola R, Gremse F, Theek B, Ehling J, Moeckel D, Hermanns-Sachweh B, Pechar M, Ulbrich K, Hennink WE, Storm G, Lederle W, Kiessling F, and Lammers T. Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines. Nano Lett. 2014;14(2):972‑81.

Reviews / Perspectives

    1. Crielaard BJ, Lammers T, and Rivella S. Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Feb 03. doi: 10.1038/nrd.2016.248 [Epub ahead of print]

    1. Hare JI, Lammers T, Ashford MB, Puri S, Storm G, and Barry ST. Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. Adv Drug Deliv Rev. 2017;108:25‑38.

    1. Mitragotri S, Lammers T, Bae YH, Schwendeman S, De Smedt S, Leroux J, Peer D, Kwon IC, Harashima H, Kikuchi A, Oh Y, Torchilin V, Hennink W, Hanes J, and Park K. Drug Delivery Research for the Future: Expanding the Nano Horizons and Beyond. J Control Release. 2017;246:183‑184.

    1. Lammers T, Kiessling F, Ashford M, Hennink W, Crommelin D, and Storm G. Cancer nanomedicine: Is targeting our target? Nat Rev Mater. 2016;1(9).

    1. Kunjachan S, Ehling J, Storm G, Kiessling F, and Lammers T. Noninvasive Imaging of Nanomedicines and Nanotheranostics: Principles, Progress, and Prospects. Chem Rev. 2015;115(19):10907‑37.

Group members

Zaheer Ahmed

Zaheer (M.Sc. Life Science, Hanyang University, South Korea, 2015) works on the development of targeted nanoparticles for the treatment of cancers. The underlying purpose of his DAAD fellowship is to harness the potential of inorganic nanoparticles such as nanoceria and to employ them to improve the efficacy and reduce the toxicity of anticancer therapy.

Z. Ahmed

Lia Appold

Lia (M.Sc. Chemistry, RWTH Aachen, 2013) works on the synthesis and characterization of model drug-loaded MB. She furthermore develops strategies and analytical techniques to PEGylate MB, and to accurately quantify the degree of surface functionalization, PEGylation and drug loading.

L. Appold

Sarah Baetke

Sarah (M.Sc. in Molecular Life Sciences (Oncology and Developmental Biology) from Maastricht University in 2011) works on the non-invasive visualization of tumor angiogenesis using functional and molecular ultrasound and micro-computed tomography. Her studies focus on the anti-angiogenic effects of molecularly targeted anti-inflammatory agents (e.g. chemokine-inhibitors), as well as on the role of certain genes and proteins (e.g. SFRP-1 and HRG) in tumor angiogenesis.

S. Baetke

Xiangyang Bai

Xiangyang (M.Sc. in Material Science and Engineering, 2015) conducted research on inorganic nanoparticles as novel antibiotics at The Technical Institute of Physics and Chemistry, Chinese Academy of Sciences. Currently he is performing his PhD research on the development of polymeric nanotheranostics for the treatment of cancer, via a grant funded by the China Scholarship Council (CSC).

X. Bai

Maike Baues

Maike (M.Sc. in Molecular Biotechnology, RWTH Aachen University, 2015) analyses several pharmaceutical and mechanical EPR enhancing strategies. In this context she evaluates neoadjuvant therapy inducing vessel normalization and ultrasound mediated sonoporation for their ability of improving the accumulation, macro- and microdistribution of different nanomedicines.

M. Baues

S. M. Ali Dadfar

Ali (M.SC. Chemical Engineering, Polymer Science and Nanotechnology, Sharif University of Technology, December 2009) works on temperature-responsive and multi-drug-loaded liposomes for tumor targeted combination therapy. In addition, he also participates in project on drug-loaded polymeric micelles for theranostic application.

A. Dadfar

Anshuman Dasgupta

Anshuman (B.Sc. in Pharmacy, BITS Pilani, India) works on a project aiming to improve drug delivery across the blood-brain barrier. He is particularly interested in the synthesis and functionalization of microbubbles, to facilitate their use for ultrasound-mediated sonoporation.

A. Dasgupta

Dr. Josef Ehling

Josef (Dr. med., RWTH Aachen University, 2011) establishes methods for non-invasively visualizing and quantifying tumor angiogenesis. In close cooperation with the Biological Mechanisms of Tumor Angiogenesis and Metastasis group, he focuses on the optimization of functional and molecular ultrasound, as well as on anatomical and functional micro-computed tomography, for assessing the efficacy of anti-angiogenic and anti-inflammatory agents. He is also involved in studies focusing on the diagnosis and treatment liver fibrosis and lung cancer metastases.

Dr.J. Ehling

Susanne Golombek

Susanne (M.Sc. in Molecular Biotechnology, RWTH Aachen University, 2013) works on the evaluation of different nanomedicines to improve their function in combined anticancer therapy. In this context she characterizes different tumor models regarding the EPR effect. In addition she participates in several studies on particle toxicity and the visualization and design of patient-customized implants.

S. Golombek

Mengjiao Liu

Mengjiao (M.Sc. in Pharmaceutics, Sichuan Agricultural University, China 2015) obtained a stipend from the China Scholarship Council (CSC) to join the Nanomedicine and Theranostics group. The primary aim of her work is to develop multifunctional microbubbles to enhance drug delivery across the blood-brain barrier (BBB) and to improve the treatment of brain tumors.

M. Liu

Federica De Lorenzi

Federica (M.Sc. Pharmaceutical Chemistry and Technology, University of Urbino, Italy 2016) focuses on the preclinical evaluation of different nanomedicines regarding their efficiency to target breast cancer metastasis. In this context, she employs various in vitro and in vivo imaging techniques to monitor and visualize metastatic lesions, to investigate the tumor microenviroment and to assess the efficacy of antimetastatic therapy.

F. De Lorenzi

Birgit Mardak

Birgit works as a technician (MTA) in the Nanomedicines and Theranostics group. She contributes to diagnostic and therapeutic experiments by working in cell culture, immunohistochemistry and microscopy. She assists students (interns, MSc and PhD students) in their work.

B. Mardak

Jan-Niklas May

Jan-Niklas (B.Sc. Biology, RWTH Aachen) is a Master student, who is involved in a project regarding the analysis of particle accumulation in the brain after ultrasound mediated blood-brain barrier opening. Therefore, he uses many imaging techniques such as hybrid CT-FMT, fluorescence microscopy and multiphoton laser microscopy.

J. May

Dr. Josbart Metselaar

Josbert (Bart) (PhD in Pharmaceutics, Utrecht University, 2004) started the company Enceladus Pharmaceuticals in 2004. With the help of grants, investments and non-equity funding, he managed to perform a series of preclinical and clinical trials focusing on three different liposomal nanomedicine products. Since 2012, he has worked as a part-time assistant professor at the University of Twente. In 2015, he also took up a group leader position at RWTH Aachen, to extend his work on the development of nanomedicines for the treatment of inflammatory disorders and cancer.

Dr.J. Metselaar

Diana Möckel

Diana (B.Sc. in Bioscience and Health, HSRW Kleve) works as a lab technician and is involved in many different projects, focusing e.g. on tumor angiogenesis, on drug targeting to tumors and on liver fibrosis. She not only contributes to cell culture, immunohistochemistry and microscopy, but also to diagnostic and therapeutic in vivo and ex vivo experiments.

D. Möckel

Tarun Ojha

Tarun (M.Sc. in Nanoscience and MTech in Nanotechnology, Amity University, India 2013) focuses on the evaluation of nanomedicine formulations in tumors with different levels of EPR. He evaluates methods to monitor and modulate angiogenesis, including vascular normalization, in order to improve drug targeting to tumors, and to enhance the efficacy of combination therapies.

T. Ojha

Vertika Pathak

Vertika (M.Sc. in Nanoscience and M.Tech in Nanotechnology, Amity University, India 2013) works on materials and methods to improve drug and oxygen delivery to tumors, in particular to brain tumors. The primary focus of her work is on alleviating tumor-associated hypoxia, via strategies such as nanomedicine-mediated vascular normalization, in order to improve the efficacy of combined modality anticancer therapy.

V. Pathak

Dr. Yang Shi

Yang obtained a PhD in pharmaceutics from Utrecht University in 2014. Afterwards, he worked as an Associate Professor at South China University of Technology in Guangzhou. Since 2016, he has been appointed as a Group Leader at The Institute for Experimental Molecular Imaging (ExMI) at RWTH Aachen University Hospital and at the Helmholtz Institute for Biomedical Engineering. His research focuses on synthetic polymers for image-guided drug delivery. His research activities include design and synthesis of amphiphilic block copolymers self-assembling into core-shell nanoparticles, which are loaded with hydrophobic therapeutic agents, and are labeled with diagnostic agents to enable in vivo visualization.

Dr.Y. Shi

Okan Tezcan

Okan (M.Sc. in Biology, Middle East Technical University, Ankara, 2013) received a prestigious DAAD scholarship to work on the relationship between multidrug resistance and metastasis. He generates multidrug resistant cells and metastatic tumor models, develops nanomedicine formulations to overcome multidrug resistance in metastases, and employs imaging techniques to longitudinally monitor therapeutic efficacy.

O. Tezcan

Benjamin Theek

Benjamin (M.Sc. in Biomedical Engineering, RWTH Aachen University, 2011) focuses on the design and evaluation of polymeric and liposomal nanomedicines for vascular normalization, in order to improve the efficacy of combined modality anticancer therapy. In addition, he develops methods for using ultrasound-based perfusion monitoring to reduce the interindividual variability in image-guided drug delivery and tumor targeting studies. Furthermore, he is involved in several different studies focusing on (theranostic) microbubbles, angiogenesis and liver fibrosis.

B. Theek

Robert Tungadi

Robert (M.Sc. Pharmacy, Hasanuddin University, Indonesia, 2008) is working on liposome formulations for the delivery of natural compounds. His project, which primarily focuses on pharmaceutical engineering and on in vitro and in vivo testing, is funded via an Indonesian scholarship.

R. Tungadi

Larissa Yokota-Rizzo

Larissa (M.Sc. in Pharmacology, University of Campinas, 2011) obtained a prestigious DAAD stipend to work on the generation of cell lines, animal models and imaging techniques for visualizing tumor metastasis. Together with the Biological Mechanisms of Tumor Angiogenesis and Metastasis group, she combines micro-computed tomography and fluorescence-mediated tomography to monitor lung cancer metastases. In addition, using both liposomes and polymers, she aims to develop image-guided nanomedicine treatments to inhibit lung cancer metastasis.

L. Yokota-Rizzo