Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration.

Autor: Durymanov MO; Department of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, Ul. Vavilova, 34/5, 119334 Moscow, Russia., Yarutkin AV; Faculty of Biology, Moscow State University, Leninskie Gory, 1-12, 119234 Moscow, Russia., Bagrov DV; Faculty of Biology, Moscow State University, Leninskie Gory, 1-12, 119234 Moscow, Russia; Scientific Research Institute of Physical-Chemical Medicine, Ul. Malaya Pirogovskaya, 1a, 119435 Moscow, Russia., Klinov DV; Scientific Research Institute of Physical-Chemical Medicine, Ul. Malaya Pirogovskaya, 1a, 119435 Moscow, Russia., Kedrov AV; P.K. Anokhin Research Institute of Normal Physiology, Ul. Baltiyskaya, 8, 125315 Moscow, Russia., Chemeris NK; Institute of Cell Biophysics, Russian Academy of Sciences, Ul. Institutskaya, 3, 142290 Pushchino, Moscow Region, Russia., Rosenkranz AA; Department of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, Ul. Vavilova, 34/5, 119334 Moscow, Russia; Faculty of Biology, Moscow State University, Leninskie Gory, 1-12, 119234 Moscow, Russia., Sobolev AS; Department of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, Ul. Vavilova, 34/5, 119334 Moscow, Russia; Faculty of Biology, Moscow State University, Leninskie Gory, 1-12, 119234 Moscow, Russia. Electronic address: sobolev@igb.ac.ru.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2016 Jun 28; Vol. 232, pp. 20-8. Date of Electronic Publication: 2016 Apr 09.
DOI: 10.1016/j.jconrel.2016.04.011
Abstrakt: Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue. Application of nitroglycerin and losartan caused from 2- to 6-fold enhanced efficacy of polyplex-mediated gene delivery depending on the tumor model. The results obtained on polyplex behavior in tumor tissues depending on physiological state of the tumor can be relevant to optimize delivery of polyplexes and other nanomedicines with similar physicochemical properties.
(Copyright © 2016. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: