Optimizing Druggability through Liposomal Formulations: New Approaches to an Old Concept

Developing innovative delivery strategies remains an ongoing task to improve both efficacy and safety of drug-based therapy. Nanomedicine is now a promising field of investigation, rising high expectancies for treating various diseases such as malignancies. Putting drugs into liposome is an old story that started in the late 1960s. Because of the near-total biocompatibility of their lipidic bilayer, liposomes are less concerned with the safety issue related to the possible long-term accumulation in the body of most nanoobjects currently developed in nanomedicine. Additionally, novel techniques and recent efforts to achieve better stability (e.g., through sheddable coating), combined with a higher selectivity towards target cells (e.g., by anchoring monoclonal antibodies or incorporating phage fusion protein), make new liposomal drugs an attractive and challenging opportunity to improve clinical outcome in a variety of disease. This review covers the physicochemistry of liposomes and the recent technical improvements in the preparation of liposome-encapsulated drugs in regard to the scientific and medical stakes

Detection and analysis of nanoparticles in patients: A critical review of the status quo of clinical nanotoxicology

International audienceOn the cusp of massive commercialization of nanotechnology-enhanced products and services, the physical and chemical analysis of nanoparticles in human specimens merits immediate attention from the research community as a prerequisite for a confident clinical interpretationof their occurrence in the human organism. In this review, we describe the caveats in current practices of extracting and isolating nanoparticles from clinical samples and show that they do not help truly define the clinical significance of any detected exogenous nano-sized objects. Finally, we suggest a systematic way of tackling these demanding scientific tasks. More specifically, a precise and true qualitative evaluation of nanoparticles in human biological samples still remains difficult to achieve because of various technical reasons. Such a procedure is more refined when the nature of the pollutants is known, like in the case of nano-sized wear debris originating from biomedical prostheses. Nevertheless, nearly all available analytical methods provide unknown quantitative accuracy and qualitative precision due to the challenging physical and chemical nature of nanoparticles. Without trustworthy information to detect and describe the nanoparticulate load of clinical samples, it is impossible to accurately assess its pathological impact on isolated cases or allow for relevant epidemiological surveys on large populations. Therefore, we suggest that the many and various specimens stored in hospitals be used for the refinement of methods of exhaustive quantitative and qualitative characterization of prominent nanoparticles in complex human milieu

Prediction of protein corona on nanomaterials by machine learning using novel descriptors

Effective in silico methods to predict protein corona compositions on engineered nanomaterials (ENMs) could help elucidate the biological outcomes of ENMs in biosystems without the need for conducting lengthy experiments for corona characterization. However, the physicochemical properties of ENMs, used as the descriptors in current modeling methods, are insufficient to represent the complex interactions between ENMs and proteins. Herein, we utilized the fluorescence change (FC) from fluorescamine labeling on a protein, with or without the presence of the ENM, as a novel descriptor of the ENM to build machine learning models for corona formation. FCs were significantly correlated with the abundance of the corresponding proteins in the corona on diverse classes of ENMs, including metal and metal oxides, nanocellulose, and 2D ENMs. Prediction models established by the random forest algorithm using FCs as the ENM descriptors showed better performance than the conventional descriptors, such as ENM size and surface charge, in the prediction of corona formation. Moreover, they were able to predict protein corona formation on ENMs with very heterogeneous properties. We believe this novel descriptor can improve in silico studies of corona formation, leading to a better understanding on the protein adsorption behaviors of diverse ENMs in different biological matrices. Such information is essential for gaining a comprehensive view of how ENMs interact with biological systems in ENM safety and sustainability assessments

Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue

International audienceBackground: Colorectal cancer is considered to be an environmental disease. In this context, the study of environmental risk factors associated with the presence of chemical elements is important, as well as improving our knowledge of the elemental fingerprint of tumor tissuecompared to non-cancer tissue.Aims: The objective was to evaluate the element distribution in colorectal adenocarcinoma biopsies, adjacent non-tumor tissues, and healthy controls (non-cancer colorectal biopsies including occlusion or ischemic colons).Methods: The study is a case-control study which compared the element distribution in colon biopsies from two groups of patients: with colorectal cancer and without colorectal cancer. Patients with colorectal cancer provided 2 different groups of samples: colorectal cancer biopsies and adjacent non-tumor tissues. 15 metal concentrations (Al, B, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Se, Si, Ti, V, and Zn) in colorectal biopsies were quantified by using acid digestion procedures and then inductively coupled plasma (ICP) atomic emission spectrometry.Results: A total of 104 patients were included. 76 patients in the colorectal cancer group (i.e. tumor and adjacent non-tumor tissues) and 28 patients in the healthy control group (i.e. noncancer colorectal biopsies). Among the 15 elements analyzed by ICP spectrometry, only boron, chromium, zinc, silicon, and magnesium were found in colorectal tissue at clearly detectable concentrations. Our data indicated that colorectal tumor biopsies have significantly elevated concentrations of magnesium as compared to adjacent non-tumor or healthy tissues. Zinc concentration followed the same trend but differences were not statistically significant. In addition, silicon appears to be more accumulated in colorectal cancer tissue than in healthy non-cancer tissue, while chromium was mostly found in adjacent non-tumor tissue. Conclusion: Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in colorectal tumor. Their potential role in colorectal carcinogenesis should be explored

Study of the nanoparticulate load of various human biological samples

L'analyse des nanoparticules dans les échantillons cliniques est une entreprise scientifique redoutable puisqu'il n'existe pas de procédures capables de faire face à la complexité des matrices biologiques. L'hypothèse centrale de ce travail est que la présence accrue de nanoparticules d'oxyde de métal et de métal dans le lavage pulmonaire et les fluides reproducteurs peut être associée à une maladie pulmonaire interstitielle idiopathique et à une baisse de la fertilité féminine et masculine, respectivement. Les procédures d'extraction développées dans le cadre de cette thèse ont permis de mesurer la distribution de la taille hydrodynamique des nanoparticules d'or par DLS et leur quantification par ICP-OES. En raison des rendements d'extraction obtenus et de la ségrégation réussie du bruit biologique, les nanoparticules d'or extraites pourraient être observées de manière représentative à l'échelle nanométrique. Plus précisément, l'ESB pourrait détecter les noyaux denses de particules d'or à faible grossissement, et MET et MEB pourraient être utilisés pour résoudre le diamètre et la morphologie des feret des particules, respectivement. Enfin, la corona biomoleculaire dure de la nanoparticule d'or extraite à partir de lavages pulmonaires pourrait être sondée avec AFM, AES et XPS pour acquérir des informations sur sa morphologie, composition élémentaire et chimie, respectivement. L'application de méthodologies développées sur les patients n'a pas renvoyé de données analytiques qui pourraient associer de manière positive et significative une teneur élevée en particules avec une probabilité accrue de maladies pulmonaire interstitielle idiopathiques ou avec oligospermie.The quantitative and qualitative analysis of nanoparticles in human biological samples is a daunting scientific endeavour as there are no technical procedures capable to cope with the complexity of biological matrices. The central hypothesis of this work is that the increased presence of metal and metal oxide nanoparticles in pulmonary lavage and reproductive fluids may be associated with idiopathic interstitial lung disease and declining female and male fertility, respectively. The developed extraction procedures in the context of this thesis allowed the measuring of the the hydrodynamic size distribution of gold nanoparticles by DLS and their quantitation my means of ICP-OES. Due to the achieved extraction yields and the successful segregation of biological noise, extracted gold nanoparticles could be representatively observed at the nanoscale. Specifically, BSE could detect the dense gold particle cores at low magnification, and TEM and FESEM could be used to resolve the particles’ Feret diameter and morphology, respectively. Finally, the hard biomolecular corona of extracted gold nanoparticle from pulmonary lavages could be probed with AFM, AES, and XPS to acquire information on its morphology, elemental composition, and chemistry, respectively. The application of developed methodologies on patients did not return analytical data that could positively and significantly associate an elevated particle content with increased odds of idiopathic diseases or with low sperm count

Etude de la charge nanoparticulaire de divers prélèvements biologiques

The quantitative and qualitative analysis of nanoparticles in human biological samples is a daunting scientific endeavour as there are no technical procedures capable to cope with the complexity of biological matrices. The central hypothesis of this work is that the increased presence of metal and metal oxide nanoparticles in pulmonary lavage and reproductive fluids may be associated with idiopathic interstitial lung disease and declining female and male fertility, respectively. The developed extraction procedures in the context of this thesis allowed the measuring of the the hydrodynamic size distribution of gold nanoparticles by DLS and their quantitation my means of ICP-OES. Due to the achieved extraction yields and the successful segregation of biological noise, extracted gold nanoparticles could be representatively observed at the nanoscale. Specifically, BSE could detect the dense gold particle cores at low magnification, and TEM and FESEM could be used to resolve the particles’ Feret diameter and morphology, respectively. Finally, the hard biomolecular corona of extracted gold nanoparticle from pulmonary lavages could be probed with AFM, AES, and XPS to acquire information on its morphology, elemental composition, and chemistry, respectively. The application of developed methodologies on patients did not return analytical data that could positively and significantly associate an elevated particle content with increased odds of idiopathic diseases or with low sperm count.L'analyse des nanoparticules dans les échantillons cliniques est une entreprise scientifique redoutable puisqu'il n'existe pas de procédures capables de faire face à la complexité des matrices biologiques. L'hypothèse centrale de ce travail est que la présence accrue de nanoparticules d'oxyde de métal et de métal dans le lavage pulmonaire et les fluides reproducteurs peut être associée à une maladie pulmonaire interstitielle idiopathique et à une baisse de la fertilité féminine et masculine, respectivement. Les procédures d'extraction développées dans le cadre de cette thèse ont permis de mesurer la distribution de la taille hydrodynamique des nanoparticules d'or par DLS et leur quantification par ICP-OES. En raison des rendements d'extraction obtenus et de la ségrégation réussie du bruit biologique, les nanoparticules d'or extraites pourraient être observées de manière représentative à l'échelle nanométrique. Plus précisément, l'ESB pourrait détecter les noyaux denses de particules d'or à faible grossissement, et MET et MEB pourraient être utilisés pour résoudre le diamètre et la morphologie des feret des particules, respectivement. Enfin, la corona biomoleculaire dure de la nanoparticule d'or extraite à partir de lavages pulmonaires pourrait être sondée avec AFM, AES et XPS pour acquérir des informations sur sa morphologie, composition élémentaire et chimie, respectivement. L'application de méthodologies développées sur les patients n'a pas renvoyé de données analytiques qui pourraient associer de manière positive et significative une teneur élevée en particules avec une probabilité accrue de maladies pulmonaire interstitielle idiopathiques ou avec oligospermie

Engineering two-dimensional nanomaterials to enable structure-activity relationship studies in nanosafety research

© 2020 Elsevier B.V. Emerging, two-dimensional engineered nanomaterials (2DNMs) possess unique and diverse physical and chemical properties, such as extreme aspect ratios, adjustable electronic properties as well as functional lattice defects and surface chemistry which underpin their interactions with biological systems. This perspective highlights the need for structure activity relationship (SAR) studies for key properties of emerging graphene-related and inorganic 2DNMs upon prioritization based on their potential impact and trajectory for large-scale production and applications. Further, it is discussed how a synthesis platform of microbiologically sterile, size-sorted, “model” 2DNMs with precise structure would enable SAR toxicological studies and allow for the sustainable and safe translation of 2D nanotechnology to real-world applications

Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review

The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood–testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility

Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review

International audienceThe real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood-testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility