• University of Ottawa
• Consejo Mexiquense de Ciencia y Tecnología
• Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México
• Consejo Nacional de Humanidades, Ciencias y Tecnologías

• Humans
• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Female
• Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
• Cell Line, Tumor
• Receptor, ErbB-2/metabolism
• Receptor, ErbB-2/antagonists & inhibitors
• Trastuzumab/chemistry
• Trastuzumab/pharmacology
• Apoptosis/drug effects
• Nanoparticles/chemistry
• Cell Survival/drug effects
• Polyglycolic Acid/chemistry
• Drug Carriers/chemistry
• Lactic Acid/chemistry
• Drug Delivery Systems
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology

• Magnetic resonance imaging
• biological imaging
• chemotherapy.
• iron oxide nanoparticles
• radiotherapy
• tumor therapy

• Humans
• Neoplasms/diagnostic imaging
• Neoplasms/therapy
• Neoplasms/drug therapy
• Neoplasms/diagnosis
• Theranostic Nanomedicine/methods
• Multimodal Imaging/methods
• Magnetic Iron Oxide Nanoparticles/chemistry
• Animals
• Photochemotherapy
• Magnetic Resonance Imaging

• cstb2022nscq-msx0191 Natural Science Foundation of Chongqing, China

• biomedical applications
• functionalized nanoparticles
• nanomedicine
• platinum nanoparticles

• Drug Delivery Systems
• Metal Nanoparticles/chemistry
• Metal Nanoparticles/therapeutic use
• Nanomedicine
• Nanoparticles/chemistry
• Nanotechnology
• Platinum/chemistry
• Polymers

Nanoparticles (NPs) are promising platforms for the development of diagnostic and therapeutic tools. One of the main hurdle to their medical application and translation into the clinic is the fact that they accumulate in the spleen and liver due to opsonization and scavenging by the mononuclear phagocyte system. The “protein corona” controls the fate of NPs in vivo and becomes the interface with cells, influencing their physiological response like cellular uptake and targeting efficiency. For these reasons, the surface properties play a pivotal role in fouling and antifouling behavior of particles. Therefore, surface engineering of the nanocarriers is an extremely important issue for the design of useful diagnostic and therapeutic systems. In recent decades, a huge number of studies have proposed and developed different strategies to improve antifouling features and produce NPs as safe and performing as possible. However, it is not always easy to compare the various approaches and understand their advantages and disadvantages in terms of interaction with biological systems. Here, we propose a systematic study of literature with the aim of summarizing current knowledge on promising antifouling coatings to render NPs more biocompatible and performing for diagnostic and therapeutic purposes. Thirty-nine studies from 2009 were included and investigated. Our findings have shown that two main classes of non-fouling materials (i.e., pegylated and zwitterionic) are associated with NPs and their applications are discussed here highlighting pitfalls and challenges to develop biocompatible tools for diagnostic and therapeutic uses. In conclusion, although the complexity of biofouling strategies and the field is still young, the collective data selected in this review indicate that a careful tuning of surface moieties is a pivotal step to lead NPs through their future clinical applications.

• biofouling
• diagnosis
• drug delivery
• nanoparticle
• protein corona
• therapy

• Biological interactions
• Experimental factors
• Gold
• Iron oxide
• Nanoparticles
• Standardization

• drug delivery
• endocytosis
• endosomal escape
• iron oxide nanoparticles

• FAPA Universidad de los Andes
• 689-2018 Minciencias

• M2 tumor-associated macrophage
• iron oxide nanoparticles
• magnetic resonance imaging
• mannose receptor
• tumor microenvironment

The impressive development of cancer immunotherapy in the last few years originates from a more precise understanding of control mechanisms in the immune system leading to the discovery of new targets and new therapeutic tools. Since different stages of disease progression elicit different local and systemic inflammatory responses, the ability to longitudinally interrogate the migration and expansion of immune cells throughout the whole body will greatly facilitate disease characterization and guide selection of appropriate treatment regiments. While using radiolabeled white blood cells to detect inflammatory lesions has been a classical nuclear medicine technique for years, new non-invasive methods for monitoring the distribution and migration of biologically active cells in living organisms have emerged. They are designed to improve detection sensitivity and allow for a better preservation of cell activity and integrity. These methods include the monitoring of therapeutic cells but also of all cells related to a specific disease or therapeutic approach. Labeling of therapeutic cells for imaging may be performed in vitro, with some limitations on sensitivity and duration of observation. Alternatively, in vivo cell tracking may be performed by genetically engineering cells or mice so that may be revealed through imaging. In addition, SPECT or PET imaging based on monoclonal antibodies has been used to detect tumors in the human body for years. They may be used to detect and quantify the presence of specific cells within cancer lesions. These methods have been the object of several recent reviews that have concentrated on technical aspects, stressing the differences between direct and indirect labeling. They are briefly described here by distinguishing ex vivo (labeling cells with paramagnetic, radioactive, or fluorescent tracers) and in vivo (in vivo capture of injected radioactive, fluorescent or luminescent tracers, or by using labeled antibodies, ligands, or pre-targeted clickable substrates) imaging methods. This review focuses on cell tracking in specific therapeutic applications, namely cell therapy, and particularly CAR (Chimeric Antigen Receptor) T-cell therapy, which is a fast-growing research field with various therapeutic indications. The potential impact of imaging on the progress of these new therapeutic modalities is discussed.

• MRI
• PET
• SPECT
• adoptive transfer
• cancer
• cell tracking
• immunotherapy
• tumor microenvironment

• P-selectin
• cancer targeting
• quinic acid
• tannic acid
• ultrasmall iron oxide nanoparticles

• Brain Neoplasms/diagnostic imaging
• Brain Neoplasms/drug therapy
• Brain Neoplasms/pathology
• Brain Neoplasms/secondary
• Cell Line, Tumor
• Contrast Media/chemistry
• Contrast Media/pharmacology
• Drug Delivery Systems
• Ferric Compounds/chemistry
• Ferric Compounds/pharmacology
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Magnetic Resonance Imaging
• Magnetite Nanoparticles/administration & dosage
• Magnetite Nanoparticles/chemistry
• P-Selectin/genetics
• Quinic Acid/chemistry
• Quinic Acid/pharmacology
• Surface Properties
• Tannins/chemistry
• Tannins/pharmacology

State-of-the-art applications of nanomedicine have the potential to revolutionize the diagnosis, prevention, and treatment of a range of conditions and diseases affecting women’s health. In this review, we provide a synopsis of potential applications of nanomedicine in some of the most dominant fields of women’s health: mental health, sexual health, reproductive medicine, oncology, menopause-related conditions and dementia. We explore published studies arising from in vitro and in vivo experiments, and clinical trials where available, to reveal novel and highly promising therapeutic applications of nanomedicine in these fields. For the first time, we summarize the growing body of evidence relating to the use of nanomaterials as experimental tools for the detection, prevention, and treatment of significant diseases and conditions across the life course of a cisgender woman, from puberty to menopause; revealing the far-reaching and desirable theoretical impact of nanomedicine across different medical disciplines. We also present an overview of potential concerns regarding the therapeutic applications of nanomedicine and the factors currently restricting the growth of applied nanomedicine.

• dementia
• menopause
• mental health
• nanomedicine
• oncology
• reproductive medicine
• sexual health

• Administration, Intravenous
• Animals
• Ferric Compounds/chemistry
• Ferric Compounds/metabolism
• Hot Temperature
• Liver/metabolism
• Lung/metabolism
• Magnetic Phenomena
• Male
• Mice
• Mice, Nude
• Nanoparticles/chemistry
• Nanoparticles/metabolism
• Particle Size
• Polyethylene Glycols/chemistry
• Spleen/metabolism
• Static Electricity

• P30 CA006973 NCI NIH HHS
• R01 CA194574 NCI NIH HHS

• apoptosis
• autophagy
• osteosarcoma
• spinning magnetic field
• superparamagnetic iron oxide particles

• R01 CA154846 NCI NIH HHS
• R01 CA202846 NCI NIH HHS
• U01 CA151810 NCI NIH HHS
• U01 CA198913 NCI NIH HHS

• iron oxide nanoparticle
• magnetic nanoparticles
• theranostic

• Biofabrication
• Chitosan
• Nonspecific binding
• Transglutaminase

• Breast
• contrast agent
• early detection of cancer
• humans
• magnetic resonance imaging
• magnetic resonance spectroscopy
• molecular imaging
• nanoparticles

• R01 CA154846 NCI NIH HHS
• U01 CA151810 NCI NIH HHS
• U01 CA198913 NCI NIH HHS

The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells.

Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production.

USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab.

Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

• CD133
• MRI
• USPIO
• USPIO-CD133 Ab
• molecular imaging

To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.

We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating.

The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study.

All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of human cancers in future studies.

• nonhuman primates
• self-healing
• transient harm
• uPAR-IONP

• MRI
• copolymer
• nanocomposite
• photothermal therapy
• siloxane
• surface modification

• Animals
• Cell Line, Tumor
• Humans
• Magnetic Resonance Imaging/methods
• Mice
• Nanocomposites/chemistry
• Phototherapy/methods
• Siloxanes/chemistry
• Spectroscopy, Near-Infrared/methods
• Surface Properties
• Theranostic Nanomedicine/methods
• Xenograft Model Antitumor Assays

• P30 CA046592 NCI NIH HHS
• 2P30CA046592-24 NCI NIH HHS

Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting. In vitro, molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation in vivo, where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the in vitro results, PEGylation did not influence in vivo IONP biodistribution. Thus, the results reported here indicate that the in vitro advantages of molecular targeting may not consistently extend to pre-clinical in vivo settings. These observations may have important implications for the design and clinical translation of advanced, multifunctional, IONP platforms.

• Animals
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Ferric Compounds/chemistry
• Humans
• Mice
• Nanoparticles/chemistry
• Nanoparticles/therapeutic use
• Receptor, ErbB-2/genetics
• Receptor, ErbB-2/metabolism

• P30 CA023108 NCI NIH HHS
• U54 CA151662 NCI NIH HHS
• 1U54CA151662-01 NCI NIH HHS

The massive amount of human genetic information already available has accelerated the identification of target genes, making gene and nucleic acid therapy the next generation of medicine. Nanoparticle (NP)-based anticancer gene therapy treatment has received significant interest in this evolving field. Recent advances in vector technology have improved gene transfection efficiencies of nonviral vectors to a level similar to viruses. This review serves as an introduction to surface modifications of NPs based on polymeric structural improvements and target moieties. A discussion regarding the future perspective of multifunctional NPs in cancer therapy is also included.

• cancer therapy
• gene delivery
• nanoparticle

Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with great potentials for various biomedical applications, but their biological activities are largely unknown. In the present study, we found that ferroferric oxide nanoparticles (Fe₃O₄ NPs) induced autophagy in blood cells. Both naked and modified Fe₃O₄ NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe₃O₄ NP-induced autophagy was accompanied by increased Beclin 1 and VPS34 and decreased Bcl-2, thus promoting the formation of the critical complex in autophagy initiation. Further studies demonstrated that Fe₃O₄ NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe₃O₄ NPs can induce prosurvival autophagy in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study suggests that caution should be taken when Fe₃O₄ NPs are used in blood cancer patients.

• anti-apoptosis
• autophagic pathway
• iron oxide nanoparticle

About 30% of human breast cancers are human epidermal growth factor receptor 2 (HER2)⁺. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2⁺ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clinical outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the development of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional compartimentalization, which allows to combine the specific target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photothermal ablation or in photodynamic therapy have been functionalized in order to match specificity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2⁺ breast cancer and anti-HER2 therapy, in particular deepening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2⁺ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical practice; however promising results encourage an upcoming translation of this research for the next future.

• Human epidermal growth factor receptor 2
• Human epidermal growth factor receptor 2⁺-breast cancer
• Nanomedicine
• Nanoparticle
• Targeted-therapy

• R01 CA120023 NCI NIH HHS