The Efficacy of Nanoparticle Delivery to Hypoxic Solid Tumors by ciRGD Co‐Administration Depends on Neuropilin‐1 and Neutrophil Levels

Author:

Izci Mukaddes1,Maksoudian Christy1ORCID,Gonçalves Filipa1,Pérez Gilabert Irati1,Rios Luci Carla1,Bolea‐Fernandez Eduardo2,Vanhaecke Frank2,Manshian Bella B.34,Soenen Stefaan J.14ORCID

Affiliation:

1. NanoHealth and Optical Imaging Group Department of Imaging and Pathology KU Leuven Herestraat 49 Leuven B3000 Belgium

2. Atomic & Mass Spectrometry – A&MS research group Department of Chemistry Ghent University Campus Sterre, Krijgslaan 281‐S12 Ghent 9000 Belgium

3. Translational Cell and Tissue Research Unit Department of Imaging and Pathology KU Leuven Herestraat 49 Leuven B3000 Belgium

4. Leuven Cancer Research Institute Faculty of Medical Sciences KU Leuven Herestraat 49 Leuven B3000 Belgium

Abstract

AbstractThe ability to improve nanoparticle delivery to solid tumors is an actively studied domain, where various mechanisms are looked into. In previous work, the authors have looked into nanoparticle size, tumor vessel normalization, and disintegration, and here it is aimed to continue this work by performing an in‐depth mechanistic study on the use of ciRGD peptide co‐administration. Using a multiparametric approach, it is observed that ciRGD can improve nanoparticle delivery to the tumor itself, but also to tumor cells specifically better than vessel normalization strategies. The effect depends on the level of tumor perfusion, hypoxia, neutrophil levels, and vessel permeability. This work shows that upon characterizing tumors for these parameters, conditions can be selected that can optimally benefit from ciRGD co‐administration as a means to improve NP delivery to solid tumors.

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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