Spectroscopic Assessment of Doxorubicin (DOX)-Gemcitabine (GEM) Gold Complex Nanovector as Diagnostic Tool of Galectin-1 Biomarker.

Introduction: The aim of this study is focused on the development of theranostic hybrid nanovectors based on gold-doxorubicin (DOX)-gemcitabine (GEM) complexes and their active targeting with Galectin-1 (Gal-1) as a promising therapeutic and prognostic marker in cancer. Methods: For this purpose, a gold salt (HAuCl4) interacts with antitumor drugs (DOX; GEM) by chelation and then stabilizes with dicarboxylic acid-terminated polyethylene glycol (PEG) as a biocompatible surfactant. The proposed methodology is fast and reproducible, and leads to the formation of a hybrid nanovector named GEM@DOX IN PEG-AuNPs, in which the chemo-biological stability was improved. All synthetic chemical products were evaluated using various spectroscopic techniques (Raman and UV-Vis spectroscopy) and transmission electron microscopy (TEM). Results: To conceive a therapeutic application, our hybrid nanovector (GEM@DOX IN PEG-AuNPs) was conjugated with the Galectin-1 protein (Gal-1) at different concentrations to predict and specifically recognize cancer cells. Gal-1 interacts with GEM@DOX in PEG-AuNPs, as shown by SPR and Raman measurements. We observed both dynamic variation in the plasmon position (SPR) and Raman band with Gal-1 concentration. Discussion: We identified that GEM grafted electrostatically onto DOX IN PEG-AuNPs assumes a better chemical conformation, in which the amino group (NH3+) reacts with the carboxylic (COO-) group of PEG diacide, whereas the ciclopenthanol group at position C-5' reacts with NH3+ of DOX. Conclusion: This study opens further way in order to built "smart nanomedical devices" that could have a dual application as therapeutic and diagnostic in the field of nanomedicine and preclinical studies associated.

DOTAREM (DOTA)-Gold-Nanoparticles: Design, Spectroscopic Evaluation to Build Hybrid Contrast Agents to Applications in Nanomedecine.

Introduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs. Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy. Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.

Doxorubicin (DOX) Gadolinium-Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent.

INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.

Design and Synthesis of Gold-Gadolinium-Core-Shell Nanoparticles as Contrast Agent: a Smart Way to Future Nanomaterials for Nanomedicine Applications.

INTRODUCTION: The development of biopolymers for the synthesis of Gd(III) nanoparticles, as therapeutics, could play a key role in nanomedicine. Biocompatible polymers are not only used for complex monovalent biomolecules, but also for the realization of multivalent active targeting materials as diagnostic and/or therapeutic hybrid nanoparticles. In this article, it was reported for the first time, a novel synthesis of Gd(III)-biopolymer-Au(III) complex, acting as a key ingredient of core-shell gold nanoparticles (Gd(@AuNPs). MATERIAL AND METHODS: The physical and chemical evaluation was carried out by spectroscopic analytical techniques (Raman spectroscopy, UV-visible and TEM). The theoretical characterization by DFT (density functional theory) analysis was carried out under specific conditions to investigate the interaction between the Au and the Gd precursors, during the first nucleation step. Magnetic features with relaxivity measurements at 7T were also performed as well as cytotoxicity studies on hepatocyte cell lines for biocompatibility studies. The in vivo detailed dynamic biodistribution studies in mice to characterize the potential applications for biology as MRI contrast agents were then achieved. RESULTS: Physical-chemical evaluation confirms the successful design and reaction supposed. Viabilities of TIB-75 (hepatocytes) cells were evaluated using Alamar blue cytotoxic tests with increasing concentrations of nanoparticles. In vivo biodistribution studies were then accomplished to assess the kinetic behavior of the nanoparticles in mice and characterize their stealthiness property after intravenous injection. CONCLUSION: We demonstrated that Gd@AuNPs have some advantages to display hepatocytes in the liver. Particularly, these nanoconjugates give a good cellular uptake of several quantities of Gd@NPs into cells, while preserving a T1 contrast inside cells that provide a robust in vivo detection using T1-weighted MR images. These results will strengthen the role of gadolinium as complex to gold in order to tune Gd(@AuNPs) as an innovative diagnostic agent in the field of nanomedicine.

Does Intravenous Lactated Ringer's Solution Raise Serum Lactate?

BACKGROUND: Serum lactate increases in states of severe sepsis and shock, but its interpretation may be subject to confounders. Lactated Ringer's solution (LR) is used in the resuscitation of septic patients and contains 28 mmol/L of sodium lactate. OBJECTIVES: We sought to determine if a bolus of 30 mL/kg of LR increases serum lactate levels. METHODS: In this double-blind, randomized controlled trial, 30 volunteers were assigned to receive either 30 mL/kg of intravenous LR or normal saline (NS). Serum lactate was measured before and after the fluid bolus. The primary outcome was the difference in the change in lactate between the LR and NS groups. Secondarily, we assessed the change in pH, bicarbonate, sodium, and chloride in each group. RESULTS: After 30 mL/kg of intravenous LR, the mean serum lactate level increased by 0.93 mmol/L (95% confidence interval 0.42-1.44 mmol/L). However, there was also a small increase in the mean serum lactate level in the NS group of 0.37 mmol/L (95% confidence interval -0.26 mmol/L to 1.00 mmol/L), such that there was not a statistically significant difference in the change in lactate when comparing the LR group to the NS group (p = 0.2). The NS group saw larger declines in pH and bicarbonate and greater increases in chloride compared with the LR group. CONCLUSION: In healthy individuals, a modest but significant rise in mean serum lactate was seen after a 30 cc/kg LR bolus. There was no difference in mean serum lactate when comparing a 30 mL/kg bolus of NS to LR.