Search

The demand for tailored, disease-adapted, and easily accessible radiopharmaceuticals is one of the most persistent challenges in nuclear imaging precision medicine. The aim of this work was to develop two multimodal radiotracers applicable for both SPECT and PET techniques, which consist of a gold nanoparticle core, a shell involved in radioisotope entrapment, peripherally placed targeting molecules, and biocompatibilizing polymeric sequences. Shell decoration with glucosamine units located in sterically hindered molecular environments is expected to result in nanoparticle accumulation in high-glucose-consuming areas. Gold cores were synthesized using the Turkevich method, followed by citrate substitution with linear PEG α,ω-functionalized with thiol and amine groups. The free amine groups facilitated the binding of branched polyethyleneimine through an epoxy ring-opening reaction by using PEG α,ω-diglycidyl ether as a linker. Afterwards, the glucose–PEG–epoxy prepolymer has been grafted onto the surface of AuPEG–PEI conjugates. Finally, the AuPEG–PEI–GA conjugates were radiolabeled with 99mTc or 68Ga. Instant thin-layer chromatography was used to evaluate the radiolabeling yield. The biocompatibility of non-labeled and 99mTc or 68Ga labeled nanoparticles was assessed on normal fibroblasts. The 99mTc complexes remained stable for over 22 hours, while the 68Ga containing ones revealed a slight decrease in stability after 1 hour. [ABSTRACT FROM AUTHOR]

Functional G-quartet hydrogels formed from natural guanosine cross linked with benzene-1,4-diboronic acid and Mg2+ support cell growth with no visible signs of gel degradation. [ABSTRACT FROM AUTHOR]

Transfection of nucleic acid molecules, large enough to interfere with the genetic mechanisms of active cells, can be performed by means of small carriers, able to collectively collaborate in generating cargocomplexes that could be involved in passive mechanisms of cellular uptake. The present work describes the synthesis, characterization, and evaluation of transfection efficacy of a conjugate molecule, which comprises a cyclic siloxane ring (2,4,6,8-tetramethylcyclotetrasiloxane, cD4H) as the core, and, on average, 3.76 molecules of 2 kDa polyethyleneimine (PEI) as cationic branches, with an average molecular mass of 7.3 kDa. As demonstrated by in silico molecular modeling and dynamic simulation, the conjugate molecule (cD4H–AGE–PEI) tends to adopt an asymmetric structure, specific for amphipathic molecules (confirmed by a log P value of −1.902 ± 0.06), that favors a rapid interaction with nucleic acids. The conjugate and the polyplexes with the pEYFP plasmid were proved to be non-cytotoxic, and capable of ensuring transfection yields better than 30%, on HEK 293T cell culture, superior to the value obtained using the SuperFect® reagent. We presume that the increased transfection efficacy originates in the ability of the conjugate to locally tightly encompass pDNA molecules by electrostatic interaction mediated by the short PEI branches, and consequently to expose the siloxane hydrophobic moiety, which decreases the interaction energy with the lipid layers. [ABSTRACT FROM AUTHOR]

The present study reports fullerene conjugates that act as efficient binders of double stranded DNA (dsDNA) into cytofriendly polyplexes. The conjugates are designed to generate dendrimeric structures, having C60 as the core and bearing linear or branched PEI and polyethyleneglycol (PEG) arms (∼2 kDa). Simple and reproducible synthesis pathways provided C60-PEI and C60-PEG-PEI conjugates. They were able to bind linear and plasmidic dsDNA and they form particulate polyplexes of 50 to 200 nm in diameter. The resulted polyplexes toggle between the anionic and cationic state at nitrogen to phosphorous ratios (N/P) of about 5, as revealed by their zeta potential and became colloidally stable at N/P ratios above 10, as determined by atomic force microscopy (AFM). They are electrophoretically unbreakable starting with N/P ratios of 3 and of 5 when salmon sperm DNA and pEYFP-C1 plasmid, respectively are loaded. Both C60-PEI·pEYFP and C60-PEG-PEI·pEYFP polyplexes are non-cytotoxic against HEK 293T cells in culture and exhibit transfection efficiency better than 25% (N/P ratios above 20) and 6% (N/P ratios above 60) respectively, measured by flow cytometry. For comparison, the commercial SuperFect® from Qiagen (positive control) was able to provide an efficiency of 15–20%, under similar conditions. Moreover, the C60-PEG-PEI conjugate is as performant as the positive control in terms of expression of EYFP reporter gene in cultured cells and exhibited high cytocompatibility, determining cell proliferation up to 200%. Our study proved that C60-PEG-PEI is effective vector for DNA delivery being, in addition, easily synthesizable, practically non-cytotoxic and as efficient the commercially available transfection tools. [ABSTRACT FROM AUTHOR]

Linear and cross-linked dynamic constitutional frameworks generated from reversibly interacting linear PEG/core constituents and cationic sites shed light on the dominant coiling versus linear DNA binding behaviours, closer to the histone DNA binding wrapping mechanism. [ABSTRACT FROM AUTHOR]

Dynamic constitutional frameworks, based on squalene, PEG and PEI components, reversibly connected to core centers, allow the efficient identification of adaptive vectors for good DNA transfection efficiency and are well tolerated by mammalian cells. [ABSTRACT FROM AUTHOR]

Multivalent biorecognition of lectin layers by glyconanoparticle sugar-clusters has been used to generate multilayer nanoplatform architectures in a QCM sensing setup. [ABSTRACT FROM AUTHOR]