Nanomedicines for brain diseases: where we are and where we are going.

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Lysosomal nanotoxicity: Impact of nanomedicines on lysosomal function.

Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity. Current data suggest that lysosomal dysfunction caused by nanoparticles is emerging as the most common intracellular trigger of nanotoxicity. This review analyzes prospect mechanisms of lysosomal dysfunction-mediated toxicity induced by nanoparticles. We summarized and critically assessed adverse drug reactions of current clinically approved nanomedicines. Importantly, we show that physicochemical properties have great impact on nanoparticles interaction with cells, excretion route and kinetics, and subsequently on toxicity. We analyzed literature on adverse reactions of current nanomedicines and hypothesized that adverse reactions might be linked with lysosomal dysfunction caused by nanomedicines. Finally, from our analysis it becomes clear that it is unjustifiable to generalize safety and toxicity of nanoparticles, since different particles possess distinct toxicological properties. We propose that the biological mechanism of the disease progression and treatment should be central in the optimization of nanoparticle design.

Nanostrategies to Develop Current Antiviral Vaccines.

Infectious diseases are a worldwide concern. They are responsible for increasing the mortality rate and causing economic and social problems. Viral epidemics and pandemics, such as the COVID-19 pandemic, force the scientific community to consider molecules with antiviral activity. A number of viral infections still do not have a vaccine or efficient treatment and it is imperative to search for vaccines to control these infections. In this context, nanotechnology in association with the design of vaccines has presented an option for virus control. Nanovaccines have displayed an impressive immune response using a low dosage. This review aims to describe the advances and update the data in studies using nanovaccines and their immunomodulatory effect against human viruses.

Lessons learned from the SARS-CoV-2 pandemic; from nucleic acid nanomedicines, to clinical trials, herd immunity, and the vaccination divide.

INTRODUCTION: In November 2019, the idea of a zoonotic virus crossing over to human transmission in a seafood market in Wuhan, China, and then soaring across the globe to claim over 6.3 million lives and persisting to date, seemed more like wild science fiction than a future reality. As the SARS-CoV-2 pandemic continues, it is important to hallmark the imprints the pandemic has made on science. AREAS COVERED: This review covers the biology of SARS-CoV-2, vaccine formulations and trials, the concept of 'herd resistance,' and the vaccination divide. EXPERT OPINION: The SARS-CoV-2 pandemic has changed the landscape of medicine. The rapid approval of SARS-CoV-2 vaccines has changed the culture of drug development and clinical approvals. This change is already leading to more accelerated trials. The RNA vaccines have opened the market for nucleic acid therapies and the applications are limitless - from cancer to influenza. A phenomenon that has occurred is that the low efficacy of current vaccines and the rapid mutation rate of the virus is preventing herd immunity from being attained. Instead, herd resistance is being acquired. Even with future, more effective vaccines, anti-vaccination attitudes will continue to challenge the quest for SARS-CoV-2 herd immunity.

Advances in nanomedicine for the treatment of infectious diseases caused by viruses.

Viruses have a worldwide impact on healthcare and social and economic growth because they are the largest cause of mortality due to infectious diseases. Furthermore, the long-term conventional drug use comes with substantial risks to public health, such as the rapid evolution of drug resistance and the emergence of secondary side effects. Therefore, it is necessary to develop new methods for the treatment of virus-related diseases. In this case, the use of nanomaterial-based nanomedicines possesses tremendous advantages over the traditional treatment approach. Nanomaterial-based drug delivery systems have unique features that make them promising candidates in the pursuit of therapeutic benefits. In this review, we present the various biocompatible nanomaterials that show promise as nanomedicines for anti-viral therapy. Also, we include how current developments in nanomedicine are being used to treat and prevent the most common viral illnesses such as the flu, HIV, SARS-CoV-2, monkeypox, and human papillomaviruses.

Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions.

Nanoparticles as drug delivery carriers have benefited diseases, including cancer, since the 1990s, and more recently, their promise to quickly and efficiently be mobilized to fight against global diseases such as in the COVID-19 pandemic have been proven. Despite these success stories, there are limited nanomedicine efforts for chronic kidney diseases (CKDs), which affect 844 million people worldwide and can be linked to a variety of genetic kidney diseases. In this Perspective, we provide a brief overview of the clinical status of genetic kidney diseases, background on kidney physiology and a summary of nanoparticle design that enable kidney access and targeting, and emerging technological strategies that can be applied for genetic kidney diseases, including rare and congenital kidney diseases. Finally, we conclude by discussing gaps in knowledge remaining in both genetic kidney diseases and kidney nanomedicine and collective efforts that are needed to bring together stakeholders from diverse expertise and industries to enable the development of the most relevant drug delivery strategies that can make an impact in the clinic.

Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19.

As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.

Nanodrug delivery systems for metabolic chronic liver diseases: advances and perspectives.

Nanomedicines are revolutionizing healthcare as recently demonstrated by the Pfizer/BioNTech and Moderna COVID-2019 vaccines, with billions of doses administered worldwide in a safe manner. Nonalcoholic fatty liver disease is the most common noncommunicable chronic liver disease, posing a major growing challenge to global public health. However, due to unmet diagnostic and therapeutic needs, there is great interest in the development of novel translational approaches. Nanoparticle-based approaches offer novel opportunities for efficient and specific drug delivery to liver cells, as a step toward precision medicines. In this review, the authors highlight recent advances in nanomedicines for the generation of novel diagnostic and therapeutic tools for nonalcoholic fatty liver disease and related liver diseases.

Chronic liver diseases are a growing concern for global public health since they can affect up to 25% of the global adult population. Currently, there is no effective treatment or cure for these diseases. Nanometer-sized capsules can be loaded with drugs and more accurately deliver these drugs to their sites of action. They help improve the availability of medicines to the liver and have the potential to reduce their side effects. Here, the authors discuss recent advances to explain how nanotechnology can help improve the benefits of existing medicines for liver disease therapy.

Interview: insights from a career developing and applying magnetic nanoparticles.

T Sen is a Reader in Nanomaterials Chemistry at the University of Central Lancashire (UCLan). He trained as a chemist, achieving his BSc Hons in Chemistry, MSc in Physical Chemistry and PhD in Materials Chemistry from the National Chemical Laboratory (Pune, India). Alongside his academic posting, he is an editorial board member for several journals including Nanomedicine. His work at UCLan is multidisciplinary, drawing from chemistry, material science, biology and medicine to work with industry and academic partners to address challenges in health and environmental sciences. The research group currently has three projects: magneto-optical nanocomposites for liver cancer therapeutics; the separation and identification of viral RNAs using magnetic nanoparticles in the context of coronavirus and developing multifunctional nanocomposites for the detection and separation of wastewater toxicity and treatment.

Multimodality imaging of nanoparticle-based vaccines: Shedding light on immunology.

In recent years, there have been significant innovations in the development of nanoparticle-based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near-infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one-size-fits-all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Re-envisioning the design of nanomedicines: harnessing automation and artificial intelligence.

INTRODUCTION: Interest in nanomedicines has surged in recent years due to the critical role they have played in the COVID-19 pandemic. Nanoformulations can turn promising therapeutic cargo into viable products through improvements in drug safety and efficacy profiles. However, the developmental pathway for such formulations is non-trivial and largely reliant on trial-and-error. Beyond the costly demands on time and resources, this traditional approach may stunt innovation. The emergence of automation, artificial intelligence (AI) and machine learning (ML) tools, which are currently underutilized in pharmaceutical formulation development, offers a promising direction for an improved path in the design of nanomedicines. AREAS COVERED: the potential of harnessing experimental automation and AI/ML to drive innovation in nanomedicine development. The discussion centers on the current challenges in drug formulation research and development, and the major advantages afforded through the application of data-driven methods. EXPERT OPINION: The development of integrated workflows based on automated experimentation and AI/ML may accelerate nanomedicine development. A crucial step in achieving this is the generation of high-quality, accessible datasets. Future efforts to make full use of these tools can ultimately contribute to the development of more innovative nanomedicines and improved clinical translation of formulations that rely on advanced drug delivery systems.

The potential impact of nanomedicine on COVID-19-induced thrombosis.

Extensive reports of pulmonary embolisms, ischaemic stroke and myocardial infarctions caused by coronavirus disease 2019 (COVID-19), as well as a significantly increased long-term risk of cardiovascular diseases in COVID-19 survivors, have highlighted severe deficiencies in our understanding of thromboinflammation and the need for new therapeutic options. Due to the complexity of the immunothrombosis pathophysiology, the efficacy of treatment with conventional anti-thrombotic medication is questioned. Thrombolytics do appear efficacious, but are hindered by severe bleeding risks, limiting their use. Nanomedicine can have profound impact in this context, protecting delicate (bio)pharmaceuticals from degradation en route and enabling delivery in a targeted and on demand manner. We provide an overview of the most promising nanocarrier systems and design strategies that may be adapted to develop nanomedicine for COVID-19-induced thromboinflammation, including dual-therapeutic approaches with antiviral and immunosuppressants. Resultant targeted and side-effect-free treatment may aid greatly in the fight against the ongoing COVID-19 pandemic.

Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery.

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Functional Nanomaterials: From Structures to Biomedical Applications.

In recent decades, a number of functional nanomaterials have attracted a great amount of attention and exhibited excellent performance for biomedical and pharmaceutical applications [...].

Success of nano-vaccines against COVID-19: a transformation in nanomedicine.

INTRODUCTION: The vaccines being used against COVID-19 are composed of either non-viral or viral nanoparticles (NPs). Nanotechnology-based vaccine technology was studied for its potentially transformative advancement of medicine. AREAS COVERED: NPs protect the encapsulated mRNA in vaccines, thereby enhancing the stability of the ribonucleic acids and facilitating their intact delivery to their specific targets. Compared to liposomes, lipid nanoparticles (LNPs) are unique and, through their rigid morphology and better cellular penetrability, render enhanced cargo stability. To explore nanotechnology-mediated vaccine delivery and its potential in future pandemics, we assessed articles from various databases, such as PubMed, Embase, and Scopus, including editorial/research notes, expert opinions, and collections of data from several clinical research trials. In the current review, we focus on the nanoparticulate approach of the different SARS-CoV-2 vaccines and explore their success against the pandemic. EXPERT OPINION: The mRNA-based vaccines, with their tremendous efficacy of ~95% (under phase III-IV clinical trials) and distinct nanocarriers (LNPs), represent a new medical front alongside DNA and siRNA-based vaccines.

The landscape of mRNA nanomedicine.

Messenger RNA (mRNA) is an emerging class of therapeutic agent for the prevention and treatment of a wide range of diseases. The recent success of the two highly efficacious mRNA vaccines produced by Moderna and Pfizer-BioNTech to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research. Challenges related to mRNA stability and immunogenicity, as well as in vivo delivery and the ability to cross multiple biological barriers, have been largely addressed by recent progress in mRNA engineering and delivery. In this Review, we present the latest advances and innovations in the growing field of mRNA nanomedicine, in the context of ongoing clinical translation and future directions to improve clinical efficacy.

The Promise of Emergent Nanobiotechnologies for In Vivo Applications and Implications for Safety and Security.

Nanotechnology, the multidisciplinary field based on the exploitation of the unique physicochemical properties of nanoparticles (NPs) and nanoscale materials, has opened a new realm of possibilities for biological research and biomedical applications. The development and deployment of mRNA-NP vaccines for COVID-19, for example, may revolutionize vaccines and therapeutics. However, regulatory and ethical frameworks that protect the health and safety of the global community and environment are lagging, particularly for nanotechnology geared toward biological applications (ie, bionanotechnology). In this article, while not comprehensive, we attempt to illustrate the breadth and promise of bionanotechnology developments, and how they may present future safety and security challenges. Specifically, we address current advancements to streamline the development of engineered NPs for in vivo applications and provide discussion on nano-bio interactions, NP in vivo delivery, nanoenhancement of human performance, nanomedicine, and the impacts of NPs on human health and the environment.