Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors

0490447 - ÚMCH 2019 RIV NL eng J - Článek v odborném periodiku
Theek, B. - Baues, M. - Gremse, F. - Pola, Robert - Pechar, Michal - Negwer, I. - Koynov, K. - Weber, B. - Barz, M. - Jahnen-Dechent, W. - Storm, G. - Kiessling, F. - Lammers, T.
Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors.
Journal of Controlled Release. Roč. 282, 28 July (2018), s. 25-34. ISSN 0168-3659. E-ISSN 1873-4995
Grant CEP: GA ČR(CZ) GA16-17207S
Institucionální podpora: RVO:61389013
Klíčová slova: nanomedicine * tumor targeting * vascular normalization
Obor OECD: Polymer science
Impakt faktor: 7.901, rok: 2018

Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of 10–20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl)methacrylamide). Multimodal and multiscale optical imaging was employed to show that normalizing the tumor vasculature improves the accumulation of fluorophore-labeled polymers in tumors, and promotes their penetration out of tumor blood vessels deep into the interstitium.
Trvalý link: http://hdl.handle.net/11104/0284834