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A triazine-based BODIPY trimer as a molecular viscometer.

ABSTRACT: Photophysical behaviour of a novel trimeric BODIPY rotor with a high extinction coefficient is reported. Steady state and time resolved fluorescence measurements established that the trimer could be used as a viscometer for molecular solvents, membrane-like environments and several cancer cell lines.

SUBMITTER: Raut SL

PROVIDER: S-EPMC4755388 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A triazine-based BODIPY trimer as a molecular viscometer.

Raut Sangram L SL Kimball Joseph D JD Fudala Rafal R Bora Ilkay I Chib Rahul R Jaafari Hana H Castillo Marlius K MK Smith Nicholas W NW Gryczynski Ignacy I Dzyuba Sergei V SV Gryczynski Zygmunt Z

Physical chemistry chemical physics : PCCP 20160201 6

Photophysical behaviour of a novel trimeric BODIPY rotor with a high extinction coefficient is reported. Steady state and time resolved fluorescence measurements established that the trimer could be used as a viscometer for molecular solvents, membrane-like environments and several cancer cell lines. ...[more]

PMID: 26795882

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Project description:This study aimed to identify suitable siRNA delivery systems based on flexible generation 2-4 triazine dendrimers by correlating physico-chemical and biological in vitro and in vivo properties of the complexes with thermodynamic parameters calculated using molecular modeling. The siRNA binding properties of the dendrimers and PEI 25 kDa were simulated, binding and stability were measured in SYBR Gold assays, and hydrodynamic diameters, zeta potentials, and cytotoxicity were quantified. These parameters were compared with cellular uptake of the complexes and their ability to mediate RNAi. Radiolabeled complexes were administered intravenously, and pharmacokinetic profiles and biodistribution of these polyplexes were assessed both invasively and non-invasively. All flexible triazine dendrimers formed thermodynamically more stable complexes than PEI. While PEI and the generation 4 dendrimer interacted more superficially with siRNA, generation 2 and 3 virtually coalesced with siRNA, forming a tightly intertwined structure. These dendriplexes were therefore more efficiently charge-neutralized than PEI complexes, reducing agglomeration. This behavior was confirmed by results of hydrodynamic diameters (72.0 nm-153.5 nm) and zeta potentials (4.9 mV-21.8 mV in 10 mM HEPES) of the dendriplexes in comparison to PEI complexes (312.8 nm-480.0 nm and 13.7 mV-17.4 mV in 10 mM HEPES). All dendrimers, even generation 3 and 4, were less toxic than PEI. All dendriplexes were efficiently endocytosed and showed significant and specific luciferase knockdown in HeLa/Luc cells. Scintillation counting confirmed that the generation 2 triazine complexes showed more than twofold prolonged circulation times as a result of their good thermodynamic stability. Conversely, generation 3 complexes dissociated in vivo, and generation 4 complexes were captured by the reticulo-endothelial system due to their increased surface charge. Molecular modeling proves very valuable for rationalizing experimental parameters based on the dendrimers' structural properties. Non-invasive molecular imaging predicted the in vivo fate of the complexes. Therefore, both techniques effectively promote the rapid development of safe and efficient siRNA formulations that are stable in vivo.

Dataset Information

A triazine-based BODIPY trimer as a molecular viscometer.

Publications

A triazine-based BODIPY trimer as a molecular viscometer.

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