Nanomedicines and Theranostics

Nanomedicines are submicrometer-sized carrier materials designed to improve the biodistribution of systemically administered (chemo‑) therapeutics. By delivering drugs more specifically to pathological sites, and by preventing them from accumulating in potentially endangered healthy tissues, nanomedicines aim to improve the balance between the efficacy and the toxicity of (chemo-) therapeutic interventions. Efforts in our group focus on several different nanomedicine formulations. In collaboration with the Dept. of Targeted Therapeutics at the University of Twente, with the Dept. of Pharmaceutics at Utrecht University, with the Institute of Macromolecular Chemistry at the Czech Academy of Sciences and with several colleagues at RWTH Aachen University Clinic, liposomes, polymers and micelles are being loaded with chemotherapeutics and with corticosteroids, and are being used to improve drug delivery to tumors, to sites of inflammation, to the brain, to the liver and to the kidney. A very important focus of our work is on image-guided drug delivery. By incorporating both drugs and imaging agents within a single nanomedicine formulation, drug delivery can be monitored non-invasively, drug release can be visualized and quantified, and drug efficacy can be evaluated during follow-up. Such theranostic systems and strategies hold significant potential for personalized (nano‑) medicine, and for improving and individualizing (chemo-) therapeutic treatments.

Selected publications

Research Papers
  1. Lammers T, Subr V, Peschke P, Kühnlein R, Hennink WE, Ulbrich K, Kiessling F, Heilmann M, Debus J, Huber PE, and Storm G. Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy. Br J Cancer. 2008;99(6):900‑10.
  1. Lammers T, Subr V, Ulbrich K, Peschke P, Huber PE, Hennink WE, and Storm G. Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials. 2009;30(20):3466‑75.
  1. Kunjachan S, Błauż A, Möckel D, Theek B, Kiessling F, Etrych T, Ulbrich K, van Bloois L, Storm G, Bartosz G, Rychlik B, and Lammers T. Overcoming cellular multidrug resistance using classical nanomedicine formulations. Eur J Pharm Sci. 2012;45(4):421‑8.
  1. Crielaard BJ, Rijcken CJF, Quan L, van der Wal S, Altintas I, van der Pot M, Kruijtzer JAW, Liskamp RMJ, Schiffelers RM, van Nostrum CF, Hennink WE, Wang D, Lammers T, and Storm G. Glucocorticoid-loaded core-cross-linked polymeric micelles with tailorable release kinetics for targeted therapy of rheumatoid arthritis. Angew Chem Int Ed Engl. 2012;51(29):7254‑8.
  1. Kunjachan S, Gremse F, Theek B, Koczera P, Pola R, Pechar M, Etrych T, Ulbrich K, Storm G, Kiessling F, and Lammers T. Noninvasive optical imaging of nanomedicine biodistribution. ACS Nano. 2013;7(1):252‑62.

 

Reviews / Perspectives

  1. Lammers T, and Ulbrich K. HPMA copolymers: 30 years of advances. Adv Drug Deliv Rev. 2010;62(2):119‑21.
  1. Lammers T, Aime S, Hennink WE, Storm G, and Kiessling F. Theranostic nanomedicine. Acc Chem Res. 2011;44(10):1029‑38.
  1. Lammers T, Kiessling F, Hennink WE, and Storm G. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release. 2012;161(2):175‑87.
  1. Lammers T. Nanomedicine on the move: from monotherapeutic regimens to combination therapies. Expert Rev Clin Pharmacol. 2012;5(2):105‑8.
  1. Lammers T, Rizzo LY, Storm G, and Kiessling F. Personalized nanomedicine. Clin Cancer Res. 2012;18(18):4889‑94.

Group members

Sarah (MSc 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.

Adelina (MD, University of Medicine and Pharmacy “Carol Davila”, Bucharest, 2010) uses in vivo and ex vivo US imaging to monitor the MB binding of MB to atherosclerotic plaques. Ex vivo experiments include studies in which TNFa-stimulated carotids are excised and mounted onto flow chambers, and in which the binding of antibody-targeted MB is being visualized and quantified. In vivo experiments are performed under similar conditions, as well as in wire-injury and ApoE-knockout mice. In cooperation with the Institute for Molecular Cardiovascular Research at RWTH Aachen, she furthermore works on myocardial infarction.

Josef (MD, 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.

Susanne (MSc 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.

Patrick (MD student, RWTH Aachen University) develops fluorophore-labeled microbubbles to facilitate translational molecular ultrasound studies15. In addition, together with the Probe Design for Molecular Imaging group, he develops polymer-based microbubbles containing iron oxide nanoparticles within their shell, to enable image-guided drug delivery across the blood-brain-barrier.

Sijumon (M Pharm, Mahatma Gandhi University, 2007; Research student at Central Drug Research Institute and Indian Institute of Technology-Kanpur, 2009) works on polymeric nanomedicines for drug targeting to angiogenic endothelium. Using various different optical imaging techniques, he evaluates the biodistribution and the tumor accumulation of passively and actively targeted fluorophore-labeled HPMA copolymers. In addition, he focuses on theranostic systems and strategies for anticancer therapy, as well as on the ability of nanomedicine formulations to overcome multidrug resistance.

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.

Diana (BSc student in Bioscience and Health, HSRW Kleve) works as a technician (BTA) in the Nanomedicines and Theranostics group. She 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.

Benjamin (MSc 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.

Zhuojun (Dipl.- Biol., RWTH Aachen, 2011) establishes in vivo and ex vivo imaging techniques – based primarily on two-photon laser scanning microscopy – to evaluate the binding of antibody-targeted MB to atherosclerotic plaques. In close cooperation with Adelina Curaj and Prof. Marc van Zandvoort (IMCAR and Maastricht University), he also develops strategies to combine TPLSM and US to monitor the progression of atherosclerosis. Furthermore, together with Patrick Koczera and Stanley Fokong, he uses fluorophore-labeled MB to evaluate (model) drug targeting to angiogenic tumor endothelium, as well as drug release from MB.

Larissa (MSc 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.