Obiettivo The aim of my proposal is to establish ‘Neoadjuvant Nanomedicines for vascular Normalization’ (NeoNaNo) as a novel concept for improving the efficacy of combined modality anticancer therapy. This concept is radically different from all other drug targeting approaches evaluated to date, since nanomedicines are not used to directly improve drug delivery to tumors, but to normalize the tumor vasculature, and to thereby indirectly improve drug (and oxygen) delivery. The need for such an alternative concept can be exemplified by taking the (pre-) clinical performance of nanomedicines into account: whereas in animal models, they generally improve both the efficacy and the tolerability of chemotherapeutic drugs, in patients, they often only attenuate the toxicity of the intervention, and they fail to improve the efficacy of the drug. To overcome this shortcoming, I here propose to use corticosteroid-containing nanomedicines, targeted to tumor-associated macrophages (TAM), to inhibit pro-inflammatory and pro-angiogenic signaling by TAM, and to thereby homogenize the tumor vasculature, increase tumor perfusion and reduce the interstitial fluid pressure. As a result of this, the tumor accumulation, intratumoral distribution and antitumor efficacy of subsequently administered chemotherapeutics, as well as of radiotherapy (because of enhanced oxygen delivery) can be substantially improved. To achieve these goals, liposomal, polymeric and micellar corticosteroids, several different animal models, and several different imaging agents and techniques will be used to (I) visualize and optimize nanomedicine-mediated vascular normalization; to (II) potentiate chemotherapy; and to (III) potentiate radiotherapy. These efforts will not only provide a solid basis for a completely new paradigm in nanomedicine research, but they will also result in novel, broadly applicable and clinically highly relevant combination regimens for improving the treatment of advanced solid malignancies. Campo scientifico medical and health sciencesmedical biotechnologynanomedicine Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Invito a presentare proposte ERC-2012-StG_20111109 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante UNIVERSITAETSKLINIKUM AACHEN Contributo UE € 1 356 000,00 Indirizzo Pauwelsstrasse 30 52074 Aachen Germania Mostra sulla mappa Regione Nordrhein-Westfalen Köln Städteregion Aachen Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Twan Gerardus Gertrudis Maria Lammers (Dr.) Contatto amministrativo Volker Legewie (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITAETSKLINIKUM AACHEN Germania Contributo UE € 1 356 000,00 Indirizzo Pauwelsstrasse 30 52074 Aachen Mostra sulla mappa Regione Nordrhein-Westfalen Köln Städteregion Aachen Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Twan Gerardus Gertrudis Maria Lammers (Dr.) Contatto amministrativo Volker Legewie (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato