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.

Correction: Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine.

[This corrects the article DOI: 10.1039/D1NA00444A.].

Correction: Factors impacting the aggregation/agglomeration and photocatalytic activity of highly crystalline spheroid- and rod-shaped TiO2 nanoparticles in aqueous solutions.

Correction for 'Factors impacting the aggregation/agglomeration and photocatalytic activity of highly crystalline spheroid- and rod-shaped TiO2 nanoparticles in aqueous solutions' by Thomas Degabriel, Elodie Colaço et al., Phys. Chem. Chem. Phys., 2018, 20, 12898-12907, https://doi.org/10.1039/C7CP08054A.

NFL-TBS.40-63 Peptide Gold Complex Nanovector: A Novel Therapeutic Approach to Increase Anticancer Activity by Breakdown of Microtubules in Pancreatic Adenocarcinoma (PDAC).

The role of the NFL-TBS.40-63 peptide is to destroy the microtubule network of target glioma cancer cells. Recently, we have conceived a gold-complex biotinylated NFL-TBS.40-63 (BIOT-NFL) to form a hybrid gold nanovector (BIOT-NFL-PEG-AuNPs). This methodology showed, for the first time, the ability of the BIOT-NFL-PEG-AuNPs to target the destruction of pancreatic cancer cells (PDAC) under experimental conditions, as well as detoxification and preclinical therapeutic efficacy regulated by the steric and chemical configuration of the peptide. For this aim, a mouse transplantation tumor model induced by MIA-PACA-2 cells was applied to estimate the therapeutic efficacy of BIOT-NFL-PEG-AuNPs as a nanoformulation. Our relevant results display that BIOT-NFL-PEG-AuNPs slowed the tumor growth and decreased the tumor index without effects on the body weight of mice with an excellent antiangiogenic effect, mediated by the ability of BIOT-NFL-PEG-AuNPs to alter the metabolic profiles of these MIA-PACA-2 cells. The cytokine levels were detected to evaluate the behavior of serum inflammatory factors and the power of BIOT-NFL-PEG-AuNPs to boost the immune system.

Correction: CTL-doxorubicin (DOX)-gold complex nanoparticles (DOX-AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model.

[This corrects the article DOI: 10.1039/D0NA00758G.].

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.

Cell penetrating peptide (CPP) gold(iii) - complex - bioconjugates: from chemical design to interaction with cancer cells for nanomedicine applications.

This study promotes an innovative synthesis of a nanotheragnostic scaffold capable of targeting and destroying pancreatic cancer cells (PDAC) using the Biotinylated NFL-TBS.40-63 peptide (BIOT-NFL), known to enter various glioblastoma cancer cells (GBM) where it specifically destroys their microtubule network. This recently proposed methodology (P7391FR00-50481 LIV) applied to other peptides VIM (Vimentin) and TAT (Twin-Arginine Translocation) (CPP peptides) has many advantages, such as targeted selective internalization and high stability under experimental conditions, modulated by steric and chemical configurations of peptides. The successful interaction of peptides on gold surfaces has been confirmed by UV-visible, dynamic light scattering (DLS), Zeta potential (ZP) and Raman spectroscopy analyses. The cellular internalization in pancreatic ductal adenocarcinoma (PDAC; MIA PACA-2) and GBM (F98) cells was monitored by transmission electron microscopy (TEM) and showed a better cellular internalization in the presence of peptides with gold nanoparticles. In this work, we also evaluated the power of these hybrid peptide-nanoparticles as photothermal agents after cancer cell internalization. These findings envisage novel perspectives for the development of high peptide-nanotheragnostics.

Correction to "Idarubicin-Gold Complex: From Crystal Growth to Gold Nanoparticles".

[This corrects the article DOI: 10.1021/acsomega.0c04501.].

Correction to "Thiol-Poly(Sodium Styrenesulfonate) (PolyNaSS-SH) Gold Complexes: From a Chemical Design to a One-Step Synthesis of Hybrid Gold Nanoparticles and Their Interaction with Human Proteins".

[This corrects the article DOI: 10.1021/acsomega.0c00376.].

Flavin Adenine Dinucleotide (FAD) Pegylated (PEG)-Complexes: Proof of Concept (PoC) of theranostic tool on a Murine Breast Cancer Model.

Flavin adenine dinucleotide (FAD) plays a key role in an extensive range of cellular oxidation-reduction reactions, which is engaged in metabolic pathways. The purpose of this study was to realize pegylated flavins formulation, named FAD and FAD-PEG diacid complex as theranostic tool in cancer therapy. For this objective, a murine breast cancer model, which was induced by mouse-derived4T1 breast cancer cells was studied to assess the therapeutic efficacy of FAD (named NP1) and FAD-PEG diacid complex (named NP2). The cytokines were monitored to evaluate the serum inflammatory factors to develop the blood cell content of different groups of nude mice. The experimental model shows that an intravenous injection of FAD (NP1) can significantly reduce tumour volume, tumour index and thymus index, and decrease neutrophils (NE), monocytes (MO), eosinophils (EO), and basophils (BA). At the same time, the content of IL-1α, IL-12P70, TNF α, IL-1ß and IL-6 was significantly reduced, and the content of IL-10 was significantly increased. These results provide the proof-of-concept for FAD as a smart adjuvant for cancer therapy and encourages their further development in the field of Nanomedicine.

Development of extracellular vesicle-based medicinal products: A position paper of the group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France".

Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective. Recent papers, provide important guidance on regulatory aspects of pharmaceutical development, defining EVs for therapeutic applications and critical considerations for the development of potency tests. In addition, the ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics as well as the Exosomes Committee from the ISCT are expected to contribute in an active way to the development of EV-based medicinal products by providing update on the scientific progress in EVs field, information to patients and expert resource network for regulatory bodies. The contribution of our work group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France", created in 2020, can be positioned in complement to all these important initiatives. Based on complementary scientific, technical, and medical expertise, we provide EV-specific recommendations for manufacturing, quality control, analytics, non-clinical development, and clinical trials, according to current European legislation. We especially focus on early phase clinical trials concerning immediate needs in the field. The main contents of the investigational medicinal product dossier, marketing authorization applications, and critical guideline information are outlined for the transition from research to clinical development and ultimate market authorization.

New insight into the aptamer conformation and aptamer/protein interaction by surface-enhanced Raman scattering and multivariate statistical analysis.

We study the interaction between one aptamer and its analyte (the MnSOD protein) by the combination of surface-enhanced Raman scattering and multivariate statistical analysis. We observe the aptamer structure and its evolution during the interaction under different experimental conditions (in air or in buffer). Through the spectral treatment by principal component analysis of a large set of SERS data, we were able to probe the aptamer conformations and orientations relative to the surface assuming that the in-plane nucleoside modes are selectively enhanced. We demonstrate that the aptamer orientation and thus its flexibility rely strongly on the presence of a spacer of 15 thymines and on the experimental conditions with the aptamer lying on the surface in air and standing in the buffer. We reveal for the first time that the interaction with MnSOD induces a large loss of flexibility and freezes the aptamer structure in a single conformation.

A Pegylated Flavin Adenine Dinucleotide PEG Complex to Boost Immunogenic and Therapeutic Effects in a Liver Cancer Model.

Flavin adenine dinucleotide (FAD) is engaged in several metabolic diseases. Its main role is being a cofactor essential for the activity of many flavoproteins, which play a crucial role in electron transport pathways in living systems. The aim of this study was to apply a pegylated flavins formulation named FAD-PEG diacide complex as theranostic pathway in cancer therapy. For this purpose, a mouse liver cancer model induced by Hepa1-6 cells was used to evaluate the therapeutic efficacy of FAD (named NP1) and FAD-PEG diacide complex (named NP2). The cytokines were applied to screen the serum inflammatory factors, to establish the blood cell content of different groups of nude mice. The highlights follows that FAD formulations (NP1; NP2) significantly suppressed the tumor growth and reduced the tumor index without effects on the body weight of mice. Furthermore, NP2 significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 (P70). The reported results provide the proof-of-concept for the synthesis of a smart adjuvant for liver cancer therapy and support their further development in the field of nanomedicine.

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.