Radioisótopos e sociedade : o legado de Marie Curie 100 anos depois

No ano em que se comemora o centenário da atribuição do Prémio Nobel da Química a Marie Curie e o Ano Internacional da Química, é oportuno recordar e analisar a herança deixada à Humanidade por esta cientista excepcional. Trata-se de um legado que não só revolucionou a ciência como igualmente teve impactos profundos e incontornáveis na sociedade. A aplicação clínica dos radioisótopos, por ela e por Pierre Curie preconizada, constitui uma das armas mais poderosas para o combate ao cancro actualmente disponíveis

Triaza-based amphiphilic chelators : synthetic route, in vitro characterization and in vivo studies of their Ga(III) and Al(III) chelates

Radiogalium chelates are important for diagnostic imaging in nuclear medicine (PET and ƴ-scintigraphy). Micelles are adequate colloidal vehicles for the delivery of therapeutic and diagnostic agents to organs and tissues. In this paper we describe the synthesis and in vitro and in vivo studies of a series of micelles-forming Ga(III) chelates targeted for the liver. The amphiphilic ligands are based on NOTA (NOTA = 1,4,7-triazacyclonoane-N,N’N’’-triacetic acid) and bear a α-alkyl chain in one of the pendant acetate arms (the size of the chain changes from four to fourteen carbon atoms). A multinuclear NMR study (1H, 13C, 27Al and 71Ga) gave some insights into the structure and dynamics of the metal chelates in solution, consistent with their rigidity and octahedral or pseudo-octahedral geometry. The critical micellar concentration of the chelates was determined using a fluorescence method and 27Al NMR spectroscopy (Al(III) was used as a surrogate of Ga(III)), both showing similar results and suggesting that the chelates of NOTAC6 form pre-micellar aggregates. The logP (octanol-water) determination showed enhancement of the lipophilic character of the Ga(III) chelates with the increase of the number of carbons in the α-alkyl chain. Biodistribution and Ƴ-scintigraphic studies of the 67Ga(III) labeled chelates were performed on Wistar rats, showing higher liver uptake for [67Ga](NOTAC8) in comparison to [67Ga](NOTAC6), consistent with a longer α-alkyl chain and a higher lipophilicity. After 24 hours both chelates were completely cleared off from the tissues and organs with no deposition in the bones and liver/spleen. [67Ga](NOTAC8) showed high kinetic stability in blood serum.Fundação para a Ciência e a Tecnologia (FCT

Entrapment of CdTe quantum dots in polymeric micelles

Semiconductor quantum dots (QDs) have attracted increasing interest to their unique sizedependent optical and electronic properties. Some of the most promising applications are imaging and biological sensing, acting as fluorescent probes.[1] However, for these purposes QDs need to be attached to other species. Thus, amphiphilic polymers, displaying both hydrophobic and hydrophilic regions, are interesting systems to encapsulate QDs.[2] The entrapment of hydrophobic QDs into surfactant micelles results in the formation of fluorescent nanoparticles composed by a QD core and a surfactant shell. This results in improved QDs dispersion in biological environments, lowering their toxicity. The present work investigates the entrapment of CdTe QDs in micelles formed by poly(acrylic acid) macroRAFT (PAA), a new water soluble amphiphilic polymer. The results obtained indicate that the PAA/QDs ration plays an important role not only in the dispersion of the nanoparticles in aqueous systems but also in the optical properties of the QDs

Polymeric micellar drug carriers with fluorescent properties

Self-assembling polymeric surfactants, based on amphiphilic block copolymers into nanosized aggregates in aqueous solution, are of great interest in the biomedical fields as one class of promising carrier systems, for drug delivery, gene therapy and diagnostic biosensors.[1] The incorporation of fluorescent probes into polymeric micelles has been fulfilled either by physically encapsulation or chemically attachment of fluorophores. [2] These micelle-based fluorescent probes not only facilitate better dispersion of fluorophores in biological environments, but also reduce their cytotoxicity by avoiding direct contact with normal cells or tissues. In this work we present new water soluble amphiphilic polymers, poly(acrylic acid) macroRAFT (PAA) 1 and poly(acrylic acid)-block-poly(9-vinylanthracene) (PAA-b-P9VA) 2, for the production of the mixed fluorescent micelles. Fluorescence assays were performed to monitoring the effect of their ratio on the formation of mixed micelles and to determine 1’s critical micelle concentration (cmc). The cmc was also evaluated by surface tension measurements

Thermodynamic stability and relaxation studies of small, triaza-macrocylic Mn(II) chelates

Due to its favorable relaxometric properties, Mn2+ is an appealing metal ion for magnetic resonance imaging (MRI) contrast agents. This paper reports the synthesis and characterization of three new triazadicarboxylate-type ligands and their Mn2+ chelates (NODAHep, 1,4,7-triazacyclononane-1,4-diacetate-7-heptanil; NODABA, 1,4,7-triazacyclononane-1,4-diacetate-7-benzoic acid; and NODAHA (1,4,7-triazacyclononane-1,4-diacetate-7-hexanoic acid). The protonation constants of the ligands and the stability constants of the chelates formed with Mn2+ and the endogenous Zn2+ ion have been determined by potentiometry. In overall, the thermodynamic stability of the chelates is lower than that of the corresponding NOTA analogues (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate), consistent with the decreased number of coordinating carboxylate groups. Variable temperature 1H NMRD and 17O NMR measurements have been performed on the paramagnetic chelates to provide information on the water exchange rates and the rotational dynamics. The values of the 17O chemical shifts are consistent with the presence of one water molecule in the first coordination sphere of Mn2+. The three complexes are in the slow to intermediate regime for the water exchange rate, and they all display relatively high rotational correlation times, which explain the relaxivity values between 4.7 and 5.8 mM-1.s-1 (20 MHz and 298 K). These relaxivities are higher than expected for Mn2+ chelates of such size and comparable to those of small monohydrated Gd3+ complexes. The amphiphilic [Mn(NODAHep)] forms micelles above 22 mM (its critical micellar concentration was determined by relaxometry and fluorescence), and interacts with HSA via its alkylic carbon chain providing a 60% relaxivity increase at 20 MHz due to a longer tumbling time.We thank the financial support from Fundacao para a Ciencia e a Tecnologia (F.C.T.), Portugal and Fundo Social Europeu (FSE) (PhD grant SFRH/BD/63639/2009 and Rede Nacional de RMN (REDE/1517/RMN/2005) for the acquisition of the Bruker Avance III 400 NMR spectrometer at the University of Minho), as well as financial support from La Ligue Contre le Cancer, France (E. T.). This work was carried out in the frame of the COST Actions D38 "Metal Based Systems for Molecular Imaging" and TD1004 "Theragnostics Imaging and Therapy"