Search

Liposomes are effective drug delivery systems that can be functionalized with imaging contrast agents, providing both diagnosis and monitoring of disease treatment. Here we describe the design of a theranostic liposomal drug delivery system whose biodistribution can be real time imaged by contrast enhanced MRI and can achieve tandem chemotherapy drug delivery. Because T 1 relaxation of MRI depends upon the chemical structure of contrast agent as well as its interaction with neighbor environment, we rationally designed a functional liposome for in vivo T 1 enhanced MRI. The liposome shows a 36-fold higher T 1 relaxation rate over the commercial MRI contrast agent Omniscan® and a long circulation time up to 300 min in vivo . Moreover, the multifunctional liposome carries both hydrophobic and hydrophilic chemotherapeutic drugs, can synergistically enhance therapeutic effects of multiple drugs and selectively deliver them to lung tumors, leading to lower doses, toxicity and sustained release. The nanoparticles, which exhibit favorable biodistributions to tumors, offer new possibilities for the simultaneous delivery of more than one drug and the evaluation of therapeutic response in vivo by T 1 enhanced MRI. Statement of Significance Cancer cells invoke different mechanisms to resist cancer therapies, particularly when delivering a single agent in a given therapy. The combination of two (or more) thermotherapy agents provides a promising way to circumvent such situations of drug resistance, due to a favorable synergistic effect that “tricks” the drug resistance mechanism. However, challenges to the simultaneous delivery of two drugs prevail, especially with regards to the simultaneous delivery of hydrophobic and hydrophobic drugs. Furthermore, non-invasive in vivo imaging of drug distribution enables the real-time monitoring and prediction of therapeutic responses to treatment. In this study, we rationally designed a theranostic liposomal drug delivery system whose biodistribution can be imaged via T 1 -weighted MRI in real-time and can achieve tandem chemotherapy drug delivery. This original study will be of considerable use to the wider drug delivery community. [ABSTRACT FROM AUTHOR]

Abstract: Although Zn2+ ions are involved in large numbers of physiopathological processes, non-invasive detection of Zn2+ ions in opaque biological samples remains a huge challenge. Here, we developed a novel zinc-responsive hyperpolarized (HP) 129Xe-based NMR molecular sensor. This HP 129Xe-based NMR molecular sensor was synthesized by attaching 2-(diphenylphosphino) benzenamine as ligand for zinc ions to the xenon-binding supramolecular cage, cryptophane. The 129Xe NMR spectroscopy of such molecular sensor was shifted up to 6.4ppm in the presence of Zn2+ ions, which was nearly four times larger than that of the reported similar sensor. The application of the sensor would benefit low concentration detection by using indirect NMR/MRI method. The response exhibited high sensitivity and selectivity as discriminated from other six potentially competing metal ions. The application of this sensor in the analysis of zinc ions in the rat serum samples was also evaluated. The strategy is generally applicable in developing sensitive and selective sensors for quantitative determination of zinc ions. [Copyright &y& Elsevier]

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5–1.7 times that of Gd-DTPA in D2O at 25°C and 9.4 T. MR imaging of Sprague–Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65–85 min; kidney 144.9±14.5%, 199.9±25.4% at 10–30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI. [Copyright &y& Elsevier]

Two gadolinium polyoxometalates, Gd2P2W18O62 and K15[(GdO)3(PW9O34)2], have been evaluated by in vivo as well as in vitro experiments as the candidates of tissue-specific magnetic resonance imaging (MRI) contrast agents. T1-relaxivities of 28.4 mM−1·s−1 for Gd2P2W18O62 and 11.2 mM−1·s−1 for K15[(GdO)3(PW9O34)2] (400 MHz, 25 °C) were higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin were also reported. The favorable liver-specific contrast enhancement and renal excretion capability in in vivo MRI with Sprague–Dawley rats after i.v. administration of K15[(GdO)3(PW9O34)2] was demonstrated. In vivo and in vitro assay showed that K15[(GdO)3(PW9O34)2] is a promising liver-specific MRI contrast agent. However, Gd2P2W18O62 did not show the favorable quality in vivo as expected from its high relaxivity in vitro, which was attributed to low bioavailability, indicating that it is of limited value as tissue-specific MRI contrast agent. [Copyright &y& Elsevier]

Two gadolinium polyoxometalates, K9GdW10O36 and K11[Gd(PW11O39)2], have been evaluated both in vivo and in vitro as candidates for tissue-specific MRI contrast agents. T1-relaxivities of 6.89 mM−1 · s−1 for K9GdW10O36 and 5.27 mM−1 · s−1 for K11[Gd(PW11O39)2] are slightly higher than that of the commercial MRI contrast agent (Gd-DTPA). Both compounds bind with bovine serum albumin and human serum transferrin and favorable liver-specific contrast enhancement in in vivo MRI with Sprague-Dawley rats after i.v. administration has been demonstrated. Imaging studies demonstrate that the two agents have a long residence time, showing MR signal enhancement in the liver for more than 40 min, longer than commercially available contrast agents. In vivo and in vitro assays showed that GdW10 and Gd(PW11)2 are promising liver-specific MRI contrast agents and GdW10 may be used in the diagnosis of the pathological state. However, with the higher acute toxicity, the two gadolinium polyoxometalates need to be modified and studied further before clinical use. [Copyright &y& Elsevier]