The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury

Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI. We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field.

Prospects of Extracellular Vesicles in Otorhinolaryngology, Head and Neck Surgery

The diagnostic and therapeutic potential of extracellular vesicles (EVs) has been recognised in many fields of medicine for several years. More recently, it has become a topic of increasing interest in otorhinolaryngology, head and neck surgery (ORL-HNS). With this narrative review, we have aspired to determine different aspects of those nanometrically sized theranostic particles, which seem to have promising potential as biomarkers in some of the most common diseases of the ORL-HNS by being available via less invasive diagnostic methods. At the same time, a better understanding of their activity provides us with new possibilities for developing specific target treatments. So far, most research has been oriented towards the role of EVs in the progression of head and neck cancer, notably head and neck squamous cell cancer. Nonetheless, some of this research has focused on chronic diseases of the ears, nose and paranasal sinuses. However, most research is still in the preclinical or experimental phase. It therefore requires a further and more profound understanding of EV content and behaviour to utilise their nanotheranostic capacities to their fullest potential.

Surface Adsorption of the Alpha-Emitter Astatine-211 to Gold Nanoparticles Is Stable In Vivo and Potentially Useful in Radionuclide Therapy

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.

Dissecting the Inorganic Nanoparticle-Driven Interferences on Adhesome Dynamics

Inorganic nanoparticles have emerged as an attractive theranostic tool applied to different pathologies such as cancer. However, the increment in inorganic nanoparticle application in biomedicine has prompted the scientific community to assess their potential toxicities, often preventing them from entering clinical settings. Cytoskeleton network and the related adhesomes nest are present in most cellular processes such as proliferation, migration, and cell death. The nanoparticle treatment can interfere with the cytoskeleton and adhesome dynamics, thus inflicting cellular damage. Therefore, it is crucial dissecting the molecular mechanisms involved in nanoparticle cytotoxicity. This review will briefly address the main characteristics of different adhesion structures and focus on the most relevant effects of inorganic nanoparticles with biomedical potential on cellular adhesome dynamics. Besides, the review put into perspective the use of inorganic nanoparticles for cytoskeleton targeting or study as a versatile tool. The dissection of the molecular mechanisms involved in the nanoparticle-driven interference of adhesome dynamics will facilitate the future development of nanotheranostics targeting cytoskeleton and adhesomes to tackle several diseases, such as cancer.

Improvements in Gold Nanorod Biocompatibility with Sodium Dodecyl Sulfate Stabilization

Due to their well-defined plasmonic properties, gold nanorods (GNRs) can be fabricated with optimal light absorption in the near-infrared region of the electromagnetic spectrum, which make them suitable for cancer-related theranostic applications. However, their controversial safety profile, as a result of surfactant stabilization during synthesis, limits their clinical translation. We report a facile method to improve GNR biocompatibility through the presence of sodium dodecyl sulfate (SDS). GNRs (120 × 40 nm) were synthesized through a seed-mediated approach, using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant to direct the growth of nanorods and stabilize the particles. Post-synthesis, SDS was used as an exchange ligand to modify the net surface charge of the particles from positive to negative while maintaining rod stability in an aqueous environment. GNR cytotoxic effects, as well as the mechanisms of their cellular uptake, were examined in two different cancer cell lines, Lewis lung carcinoma (LLC) and HeLa cells. We not only found a significant dose-dependent effect of GNR treatment on cell viability but also a time-dependent effect of GNR surfactant charge on cytotoxicity over the two cell lines. Our results promote a better understanding of how we can mediate the undesired consequences of GNR synthesis byproducts when exposed to a living organism, which so far has limited GNR use in cancer theranostics.

Theranostic Applications of Nanoparticle-Mediated Photoactivated Therapies

Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.

Nanoscale Carbon-Polymer Dots for Theranostics and Biomedical Exploration

In recent years, new carbonized nanomaterials have emerged in imaging, sensing, and various biomedical applications. Published literature shows that carbon dots (CDs) have been explored more extensively than any other nanomaterials. However, its polymeric version, carbon polymer dots (CPDs), did not get much attention. The non-conjugated and single-particle CPDs have all the merits of polymer and CDs, such as photoluminescent properties. The partially carbonized CPDs can be applied like CDs without surface passivation and functionalization. This merit can be further enhanced through the selection of desired precursors and control of carbonization synthesis. CPDs can absorb UV-visible-NIR light and can enhance the photoresponsive chemical and biochemical interactions. This review aims to introduce this area of renewed interest and provide insights into current developments of CPDs nanoparticles and present an overview of chemical, biological, and therapeutic applications.

Deciphering Exhaled Aerosol Fingerprints for Early Diagnosis and Personalized Therapeutics of Obstructive Respiratory Diseases in Small Airways

Respiratory diseases often show no apparent symptoms at their early stages and are usually diagnosed when permanent damages have been made to the lungs. A major site of lung pathogenesis is the small airways, which make it highly challenging to detect using current techniques due to the diseases’ location (inaccessibility to biopsy) and size (below normal CT/MRI resolution). In this review, we present a new method for lung disease detection and treatment in small airways based on exhaled aerosols, whose patterns are uniquely related to the health of the lungs. Proof-of-concept studies are first presented in idealized lung geometries. We subsequently describe the recent developments in feature extraction and classification of the exhaled aerosol images to establish the relationship between the images and the underlying airway remodeling. Different feature extraction algorithms (aerosol density, fractal dimension, principal mode analysis, and dynamic mode decomposition) and machine learning approaches (support vector machine, random forest, and convolutional neural network) are elaborated upon. Finally, future studies and frequent questions related to clinical applications of the proposed aerosol breath testing are discussed from the authors’ perspective. The proposed breath testing has clinical advantages over conventional approaches, such as easy-to-perform, non-invasive, providing real-time feedback, and is promising in detecting symptomless lung diseases at early stages.

A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

Polymer-Drug Conjugates as Nanotheranostic Agents

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.