Nanomaterials In Medicine Research Articles

Material Trends and Clinical Costings in Systematically Identified CDER‐Approved Nanomedicines

AbstractResearch into mechanisms and potential applications of nanomaterials in medicine has expanded steadily in recent decades, with increasing translational focus. Development costs, including for clinical trials, are often cited as factors limiting the translational viability of novel nanomedicines, especially compared to small new molecular entities (NMEs) and therapeutic biologics. Yet, to date, there has been no systematic investigation into the clinical programs or costs of translating and commercializing nanomedicines, nor a comparison to NMEs and therapeutic biologics, to support these claims. Here, nanomedicines approved by the United States Food and Drug Administration's Center for Drug Evaluation and Research (CDER) from 2011 to 2023 are systematically identified and categorized. Nanomedicines were identified as formulations where submicron particle size contributes to product function. Like biologics and NMEs, nanomedicines are most frequently approved for oncological indications. Notably, all anti‐cancer nanomedicines are indicated to treat orphan diseases, which is representative of the potential for nanomedicines to occupy pharmaceutical niches in treating diseases affecting smaller patient cohorts. The median estimated cost of pivotal trials for nanomedicines is 47% that of biologics and NMEs approved in the same timeframe. The findings indicate higher manufacturing costs in nanomedicine development may be mitigated by savings elsewhere, increasing translational viability.

Drug-loaded nanoparticles for cancer therapy: a high-throughput multicellular agent-based modeling study.

Interactions between biological systems and engineered nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patient's overall response. Although a number of models have explored these interactions in the past, few have focused on simulating individual cell-NP interactions. This study develops a multicellular agent-based model of cancer nanotherapy that simulates NP internalization, drug release within the cell cytoplasm, "inheritance" of NPs by daughter cells at cell division, cell pharmacodynamic response to the intracellular drug, and overall drug effect on tumor dynamics. A large-scale parallel computational framework is used to investigate the impact of pharmacokinetic design parameters (NP internalization rate, NP decay rate, anticancer drug release rate) and therapeutic strategies (NP doses and injection frequency) on the tumor dynamics. In particular, through the exploration of NP "inheritance" at cell division, the results indicate that cancer treatment may be improved when NPs are inherited at cell division for cytotoxic chemotherapy. Moreover, smaller dosage of cytostatic chemotherapy may also improve inhibition of tumor growth when cell division is not completely inhibited. This work suggests that slow delivery by "heritable" NPs can drive new dimensions of nanotherapy design for more sustained therapeutic response.

Applications of nanomaterials in medicine against cancer

Nowadays, all walks of life are developing with innovation at their core, and the subject of materials is no exception, while nanomaterials occupy an important position in the emerging field due to their unique properties and wide coverage. In addition, the incidence of cancer, a difficult disease with a very high mortality rate, is increasing day by day. Therefore, research on cancer has received extensive attention from society. Therefore, this paper explores how cancer can be treated by means of nanomaterials through the organization of current research and papers in the field. Research at this stage suggests that nanomaterials play a major auxiliary role in anti-cancer technology, as follows: enhancing the ability of other substances to disrupt cell membranes, assisting in the delivery of anti-tumor drugs, improving imaging capabilities, and enhancing the ability of some substances to inhibit tumor growth through specific mechanisms. In future research, the focus will be on minimizing the side effects of the treatment and improving its safety.

Applications of quartz crystal microbalance with dissipation in nanomedicine (QCM-D): a personal experience

Due to their unique physical and chemical properties, the potential application of nanomaterials in medicine is partic¬ularly attractive. Despite the many advantages that nanomaterials can offer as diagnostic and therapeutic tools, their transition from the bench to clinical practice is extremely challenging. One of the many barriers that nanomedicines may encounter is their toxicological effect. In fact, the development of novel nanomaterials / nanoparticles must pro¬ceed always in tandem with the assessment of any potential toxicological effects associated to them. Once nano¬materials reach the systemic circulation, they interact with endothelial cells, plasma proteins, and other blood compo¬nents. There is no doubt that the study of nanomaterials-blood interactions is crucial to warrant the biocompatibility of nanomaterials developed for human use.

Enhanced bone regeneration with bioprinted GelMA/Bentonite scaffolds inspired by bone matrix

ABSTRACT In bone tissue engineering, the search for improved repair methods is crucial, given the drawbacks of traditional strategies like donor site issues and immune rejection. Addressing these challenges, this paper introduces an innovative GelMA/Bentonite composite bioink for 3D bioprinting, designed to create scaffolds that closely emulate native bone tissue. GelMA is selected for its biocompatibility and modifiable mechanics, while Bentonite's mineral richness and ion exchange capacity are harnessed to enhance scaffold structure and promote an osteogenic microenvironment. This research marks the inaugural incorporation of Bentonite into a bioink, a significant stride forward given its established safety in pharmaceuticals and versatility across industries. This bioink formulation signifies a breakthrough in bone tissue engineering, aiming to improve the osteointegration and regeneration of bone tissue. Combining Bentonite with GelMA marks a key step in creating bioinks that enhance bone healing, potentially transforming scaffold-based bone regeneration and pioneering the use of natural nanomaterials in medicine.

Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Monocyte (THP-1) Response to Silver Nanoparticles Synthesized with Rumex hymenosepalus Root Extract.

The study, synthesis, and application of nanomaterials in medicine have grown exponentially in recent years. An example of this is the understanding of how nanomaterials activate or regulate the immune system, particularly macrophages. In this work, nanoparticles were synthesized using Rumex hymenosepalus as a reducing agent (AgRhNPs). According to thermogravimetric analysis, the metal content of nanoparticles is 55.5% by weight. The size of the particles ranges from 5-26 nm, with an average of 11 nm, and they possess an fcc crystalline structure. The presence of extract molecules on the nanomaterial was confirmed by UV-Vis and FTIR. It was found by UPLC-qTOF that the most abundant compounds in Rh extract are flavonols, flavones, isoflavones, chalcones, and anthocyanidins. The viability and apoptosis of the THP-1 cell line were evaluated for AgRhNPs, commercial nanoparticles (AgCNPs), and Rh extract. The results indicate a minimal cytotoxic and apoptotic effect at a concentration of 12.5 μg/mL for both nanoparticles and 25 μg/mL for Rh extract. The interaction of the THP-1 cell line and treatments was used to evaluate the polarization of monocyte subsets in conjunction with an evaluation of CCR2, Tie-2, and Arg-1 expression. The AgRhNPs nanoparticles and Rh extract neither exhibited cytotoxicity in the THP-1 monocyte cell line. Additionally, the treatments mentioned above exhibited anti-inflammatory effects by maintaining the classical monocyte phenotype CD14++CD16, reducing pro-inflammatory interleukin IL-6 production, and increasing IL-4 production.

A brief review on the nanomaterials-based detection of CKD biomarkers

Chronic kidney disease (CKD) imposes a significant worldwide medical burden, exacerbated by the often limited efficacy of current treatments. The future prevention and management of CKD critically rely on early detection and effective intervention. Nanomaterials (NMs), such as fluorescence carbon dots (CDs), quantum dots (QDs), and metal-based NMs, emerge as unique and highly sensitive probe materials expected to play a substantial role in the precise identification of CKD biomarkers. NMs’ design makes it possible to manage properties including size, shape, charge, and targeting ligands, which enhances the biological compatibility and availability of medicines. Consequently, the rise of NMs in medicine has brought about fresh approaches to CKD diagnosis. This review explores the utility of the NMs for the rapid identification of CKD biomarkers.

Nanomaterials in Medicine: Understanding Cellular Uptake, Localization, and Retention for Enhanced Disease Diagnosis and Therapy.

Nanomaterials (NMs) have emerged as promising tools for disease diagnosis and therapy due to their unique physicochemical properties. To maximize the effectiveness and design of NMs-based medical applications, it is essential to comprehend the complex mechanisms of cellular uptake, subcellular localization, and cellular retention. This review illuminates the various pathways that NMs take to get from the extracellular environment to certain intracellular compartments by investigating the various mechanisms that underlie their interaction with cells. The cellular uptake of NMs involves complex interactions with cell membranes, encompassing endocytosis, phagocytosis, and other active transport mechanisms. Unique uptake patterns across cell types highlight the necessity for customized NMs designs. After internalization, NMs move through a variety of intracellular routes that affect where they are located subcellularly. Understanding these pathways is pivotal for enhancing the targeted delivery of therapeutic agents and imaging probes. Furthermore, the cellular retention of NMs plays a critical role in sustained therapeutic efficacy and long-term imaging capabilities. Factors influencing cellular retention include nanoparticle size, surface chemistry, and the cellular microenvironment. Strategies for prolonging cellular retention are discussed, including surface modifications and encapsulation techniques. In conclusion, a comprehensive understanding of the mechanisms governing cellular uptake, subcellular localization, and cellular retention of NMs is essential for advancing their application in disease diagnosis and therapy. This review provides insights into the intricate interplay between NMs and biological systems, offering a foundation for the rational design of next-generation nanomedicines.

Current Overview of Metal Nanoparticles' Synthesis, Characterization, and Biomedical Applications, with a Focus on Silver and Gold Nanoparticles.

Metal nanoparticles (NPs) have garnered considerable attention, due to their unique physicochemical properties, that render them promising candidates for various applications in medicine and industry. This article offers a comprehensive overview of the most recent advancements in the manufacturing, characterization, and biomedical utilization of metal NPs, with a primary focus on silver and gold NPs. Their potential as effective anticancer, anti-inflammatory, and antimicrobial agents, drug delivery systems, and imaging agents in the diagnosis and treatment of a variety of disorders is reviewed. Moreover, their translation to therapeutic settings, and the issue of their inclusion in clinical trials, are assessed in light of over 30 clinical investigations that concentrate on administering either silver or gold NPs in conditions ranging from nosocomial infections to different types of cancers. This paper aims not only to examine the biocompatibility of nanomaterials but also to emphasize potential challenges that may limit their safe integration into healthcare practices. More than 100 nanomedicines are currently on the market, which justifies ongoing study into the use of nanomaterials in medicine. Overall, the present review aims to highlight the potential of silver and gold NPs as innovative and effective therapeutics in the field of biomedicine, citing some of their most relevant current applications.

Bringing pathology to nanomedicine: a comparison of in vivo toxicity of polymeric nanoparticle carriers with and without chitosan coating

Over the last years, there has been an increasing number of proposals for the use of nanomaterials in medicine. The safety of novel technologies must be verified, prior to their clinical application. Pathology has much to contribute towards this end. In this study, we compared the in vivo toxicity effects of poly- (lactic-co-glycolic acid) nanoparticles with and without chitosan shell. Both nanoparticle types were loaded with curcumin. The nanoparticles were assessed in vitro for potential cytotoxicity with cell viability studies. For the in vivo test, 36 adult Wistar rats were used, four of which were the control group. The remaining 32 were divided into 2 groups, each of which was administered differentially coated drug carriers: (A) nanoparticles without chitosan coating and (B) nanoparticles with chitosan coating. For both groups, the subcutaneous route was used for administration. Each group was further divided into 2 sub-groups of 8 animals each. The animals of the first sub-groups were sacrificed 24 h after the injection and those of the second on the 7th day. The control group was also divided into 2 subgroups of 2 animals each. At the appointed post-administrative date, the rats were sacrificed, and specimens from the brain, liver, kidneys, heart, stomach, lungs, and from the skin at the injection site were collected and studied histopathologically. The evaluation of both in vitro and in vivo testing shows that nanoparticles with chitosan have significantly less, if any, toxic effects compared to those without chitosan.

PH-Triggered Size-Transformable and Bioactivity-Switchable Self-Assembling Chimeric Peptide Nanoassemblies for Combating Drug-Resistant Bacteria and Biofilms.

Drug-resistant bacteria and biofilm-associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self-assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug-resistant bacteria and biofilm-associated infections. Notably, the chimeric peptide self-assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm-infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug-resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological-environment-driven nanostructural transformations may provide a theoretical basis for designing high-performance antibacterial nanomaterials and advance the application of peptide-based nanomaterials in medicine and animal husbandry.

Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility.

The potential use of nanomaterials in medicine offers opportunities for novel therapeutic approaches to treating complex disorders. For that reason, a new branch of science, named nanotoxicology, which aims to study the dangerous effects of nanomaterials on human health and on the environment, has recently emerged. However, the toxicity and risk associated with nanomaterials are unclear or not completely understood. The development of an adequate experimental strategy for assessing the toxicity of nanomaterials may include a rapid/express method that will reliably, quickly, and cheaply make an initial assessment. One possibility is the characterization of the hemocompatibility of nanomaterials, which includes their hemolytic activity as a marker. In this review, we consider various factors affecting the hemolytic activity of nanomaterials and draw the reader's attention to the fact that the formation of a protein corona around a nanoparticle can significantly change its interaction with the red cell. This leads us to suggest that the nanomaterial hemolytic activity in the buffer does not reflect the situation in the blood plasma. As a recommendation, we propose studying the hemocompatibility of nanomaterials under more physiologically relevant conditions, in the presence of plasma proteins in the medium and under mechanical stress.

Application of Different Nanomaterials in Biomedical Field

Nanomaterials is the most promising materials in biomedicine because many of its features can be used to go deep into places which cannot be touched by traditional treatment methods. As a result, a diverse of different nanomaterials are quickly growing to be one of the most important materials in biomedical fields. In many cases, nanomaterials show great promise in further improving the efficiency of medical treatment, where they are very beneficial for drug delivery. This research will analyze the application principles of nanomaterials and explain why and where to use nanomaterials in medicine and treatments. More specifically, this research will introduce some application status of nanomaterials in the field of biomedicine, including cancer treatment, the treatment of coronary artery disease, biomarkers detection and Nano antibacterial agents.

Nanomaterials in medicine: a concise review of nanomaterials intended to treat pathology, nanomaterials induced by pathology, and pathology provoked by nanomaterials

Nanomaterials in medicine: a concise review of nanomaterials intended to treat pathology, nanomaterials induced by pathology, and pathology provoked by nanomaterials

Use of Semiconductor Gas Sensors Made from Nanomaterials in Medicine

Use of Semiconductor Gas Sensors Made from Nanomaterials in Medicine

A Decision Support System for preclinical assessment of nanomaterials in medical products: the REFINE DSS

The application of nanomaterials in medicine has led to novel pharmaceuticals and medical devices that have demonstrated a strong potential for increasing the efficacy/performance and safety of therapeutic and diagnostic procedures to address a wide range of diseases. However, the successful translation of these technologies from their inception (proof-of-concept) to clinical practice has been challenged by substantial gaps in the scientific and technical capacity of R&D companies, especially SMEs, to keep up with the ever-evolving regulatory expectations in the emerging area of nanomedicine. To address these challenges, the EU Horizon 2020 project REFINE has developed a Decision Support System (DSS) to support developers of nanotechnology-enabled health products in bringing their products to the clinic. The REFINE DSS has been developed to support experts, innovators, and regulators in the implementation of intelligent testing strategies (ITS) for efficient preclinical assessment of nanotechnology-enabled health products. The DSS applies logical rules provided by REFINE experts which generate prioritized lists of assays to be performed (i.e. ITSs) for physicochemical characterisation and for immunotoxicological endpoints. The DSS has been tested against several case studies and was validated by internal project experts as well as external ones.Graphical abstract

Type-specific impacts of silver on the protein profile of tomato (Lycopersicon esculentum L.)

Silver nanoparticles (AgNPs) are particularly among the widely used nanomaterials in medicine, industry, and agriculture. The small size and large surface area of AgNPs and other nanomaterials result in their high reactivity in biological systems. To better understand the effects of AgNPs on plants at the molecular level, tomato (Lycopersicon esculentum L.) seedlings were exposed to 30 mg/L silver in the form of nanoparticle (AgNPs), ionic (AgNO3), or bulk (Ag0) in 50% Hoagland media for 7 days. The effects of silver on the expression of plant membrane transporters H+-ATPase, vacuolar type H+-ATPase (V-ATPase), and enzymes isocitrate dehydrogenase (IDH), and catalase in roots was assessed using RT-qPCR and immunofluorescence-confocal microscopy. We observed significantly higher expression of catalase in plants exposed to AgNPs (Fold of expression 1.1) and AgNO3 (Fold of expression 1.2) than the control group. The immunofluorescence imaging of the proteins confirmed the gene expression data; the expression of the enzyme catalase was upregulated 41, 216, and 770% higher than the control group in plants exposed to AgNPs, Ag0, and AgNO3, respectively. Exposure to AgnO3 resulted in the upregulation (fold of expression 1.2) of H+-ATPase and downregulation (fold of expression 0.7) of V-ATPase. A significant reduction in the expression of the redox-sensitive tricarboxylic cycle (TCA) enzyme mitochondrial IDH was observed in plants exposed to AgNPs (38%), AgNO3 (48%), or Ag0 (77%) compared to the control. This study shows that exposure to silver affects the expression of genes and protein involved in membrane transportation and oxidative response. The ionic form of silver had the most significant effect on the expression of genes and proteins compared to other forms of silver. The results from this study improve our understanding about the molecular effects of different forms of silver on important crop species. Novelty statement Silver nanoparticles released into the environment can be oxidized and be transformed into ionic form. Both the particulate and ionic forms of silver can be taken by plants and affect plants physiological and molecular responses. Despite the extensive research in this area, there is a scarce of information about the effects of silver nanoparticles on the expression of membrane transporters especially H+-ATPase involved in regulating cells' electrochemical charge, and the activity of enzymes involved in oxidative stress responses. This is a unique study that evaluates the expression of cellular proton transporters and enzymes of redox balance and energy metabolisms such as membrane transporters, H+-ATPase, and V-ATPases, and enzymes catalase and IDH. The results provide us valuable information about the impact of silver on plants at the molecular level by evaluating the expression of genes and proteins. Key Message The exposure of plants to silver as an environmental stressor affects the expression of genes and proteins involved in maintaining cell’s electrochemical gradient (H+-ATPase, V-ATPase) and redox potential (IDH, catalase).

Rapid synthesis and characterization of silver-loaded graphene oxide nanomaterials and their antibacterial applications.

With the promising potential application of Ag/graphene-based nanomaterials in medicine and engineering materials, the large-scale production has attracted great interest of researchers on the basis of green synthesis. In this study, water-soluble silver/graphene oxide (Ag/GO) nanomaterials were synthesized under ultrasound-assisted conditions. The structural characteristics of Ag/GO were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy and energy dispersion spectroscopy, respectively. The results showed the silver particles (AgNPs) obtained by reduction were attached to the surface of GO, and there was a strong interaction between AgNPs and GO. The antibacterial activity was primarily evaluated by the plate method and hole punching method. Antibacterial tests indicated that Ag/GO could inhibit the growth of Gram-negative and Gram-positive bacteria, special for the Staphylococcus aureus.

Synergic fabrication of succimer coated titanium dioxide nanomaterials delivery for in vitro proliferation and in vivo examination on human aortic endothelial cells

The probable nanotoxicity to human health and the environment is a significant challenge for the sustainable application of nanomaterials in medicine. The cytototoxical effect of succimer (meso-2,3-dimercaptosuccinic acid-DMSA) coated titanium dioxide (DMSA-TiO2) with cultured human aortic endothelial cells (HAoECs) was assessed in this investigation. Our findings have shown that DMSA-TiO2 can be accumulated in HAoECs and dispersed in a cytoplasm on the culture medium. DMSA-cytotoxicity TiO2 effects were dose-responsive, and the concentrations were of little toxicity, and MTT stain testing showed that they had only 0.02 mg ml−1. Meanwhile, the lactate dehydrogenase biomarker was not considerably more remarkable than the biomarker from untreated (control) cells (free DMSA-TiO2). Though, also without any apparent signs of cell damage, the endocrine functions for prostacyclin I-2 and endothelin-1 and the urea transporter functions were modified. In addition, in vitro endothelial tube development has been shown that HAoECs could induce angiogenesis even with small amounts of DMSA-TiO2 (0.01 and 0.02 mg ml−1). Further, we have examined the in vivo toxicity and biochemical parameter by animal model. Furthermore, in vivo assessments designated that the resulting DMSA-TiO2 presented synergistic activities of angiogenesis activity. Overall, these findings show the cytotoxicity of DMSA-TiO2 and could induce adverse effects on normal endothelial cells.