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Tremendous research efforts have been devoted to nanoparticles for applications in optoelectronics and biomedicine. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology because of outstanding photophysical properties, including narrow and symmetrical emission spectrum, broad fluorescence excitation spectrum, the tenability of the emission wavelength with the particle size and composition, anti-photobleaching ability and stable fluorescence. These characteristics are suitable for optical imaging, drug delivery and other biomedical applications. Research on QDs toxicology has demonstrated QDs affect or damage the biological system to some extent, and this situation is generally caused by the metal ions and some special properties in QDs, which hinders the further application of QDs in the biomedical field. The toxicological mechanism mainly stems from the release of heavy metal ions and generation of reactive oxygen species (ROS). At the same time, the contact reaction with QDs also cause disorders in organelles and changes in gene expression profiles. In this review, we try to present an overview of the toxicity and related toxicity mechanisms of QDs in different target organs. It is believed that the evaluation of toxicity and the synthesis of environmentally friendly QDs are the primary issues to be addressed for future widespread applications. However, considering the many different types and potential modifications, this review on the potential toxicity of QDs is still not clearly elucidated, and further research is needed on this meaningful topic.

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

Nanotechnology and the incorporation of nanomaterials (NM) into everyday products help to solve problems in society and improve the quality of life, allowing for major advances in the technological, industrial, and medical fields. Despite this positive and encouraging side of nanotechnology, the potential risks of NM to human health and the environment, as well as the ethical, legal, and social implications associated with nanotechnology, cannot be disregarded. Indeed, the same characteristics that make NM interesting from a technological application point of view may be undesirable upon their release into the environment. In fact, hundreds of tons of NM are released into the environment every year. The reduced dimensions of NM facilitate their diffusion into and transport through the atmosphere, water, and soil, and as well as their uptake and (bio)accumulation in organisms. Nanotoxicology has emerged as a discipline that seeks to assess the potential risk of NM, integrating knowledge and resources from material science, biology, toxicology, and analytical chemistry. Several studies have alerted us to the risks that certain NM represent for the environment and for our health, depending on their persistence and circulation in ecosystems, on the dose and responses of organisms to acute and chronic exposure to these substances, and on the ability of organisms to (bio)accumulate and/or excrete them. However, knowledge of the harmful effects of these contaminants of emerging concern is still insufficient, including mixture effects. Efforts to advance our knowledge on the reactivity of NM and their effects have been made using mostly in vitro and in vivo models; however, in recent years, in silico approaches and quantitative structure–activity relationship (QSAR) modeling have been gaining more attention. Nanotoxicity assessment using in vitro models gathers important information regarding the mechanism(s) of action of NM at the cellular and molecular levels. These models also offer the benefits of reduced costs and ethical concerns over animal welfare (3Rs principle), usually resulting in the faster toxicity screening of chemicals, an advantage considering the increasing number of materials and contaminant combinations to be tested. However, they lack the complexity and metabolic capabilities that in vivo models provide, which is important in identifying the relationship between exposure dose and the occurrence of adverse effects, and in understanding how the body handles NM in terms of their absorption, distribution, metabolism, and excretion (ADME). (...)

Nanomedicine has the potential to transform healthcare by offering targeted therapies, precise diagnostics, and enhanced drug delivery systems. The National Institutes of Health has coined the term \"nanomedicine\" to describe the use of nanotechnology in biological system monitoring, control, diagnosis, and treatment. Nanomedicine continues to receive increasing interest for the rationalized delivery of therapeutics and pharmaceutical agents to achieve the required response while reducing its side effects. However, as nanotechnology continues to advance, concerns about its potential toxicological effects have also grown. This review explores the current state of nanomedicine, focusing on the types of nanoparticles used and their associated properties that contribute to nanotoxicity. It examines the mechanisms through which nanoparticles exert toxicity, encompassing various cellular and molecular interactions. Furthermore, it discusses the assessment methods employed to evaluate nanotoxicity, encompassing in-vitro and in-vivo models, as well as emerging techniques. The review also addresses the regulatory issues surrounding nanotoxicology, highlighting the challenges in developing standardized guidelines and ensuring the secure translation of nanomedicine into clinical settings. It also explores into the challenges and ethical issues associated with nanotoxicology, as understanding the safety profile of nanoparticles is essential for their effective translation into therapeutic applications.

This review offers a systematic discussion about nanotoxicology and nanosafety associated with nanomaterials during manufacture and further biomedical applications. A detailed introduction on nanomaterials and their most frequently uses, followed by the critical risk aspects related to regulatory uses and commercialization, is provided. Moreover, the impact of nanotoxicology in research over the last decades is discussed, together with the currently available toxicological methods in cell cultures (in vitro) and in living organisms (in vivo). A special focus is given to inorganic nanoparticles such as titanium dioxide nanoparticles (TiO2NPs) and silver nanoparticles (AgNPs). In vitro and in vivo case studies for the selected nanoparticles are discussed. The final part of this work describes the significance of nano-security for both risk assessment and environmental nanosafety. “Safety-by-Design” is defined as a starting point consisting on the implementation of the principles of drug discovery and development. The concept “Safety-by-Design” appears to be a way to “ensure safety”, but the superficiality and the lack of articulation with which it is treated still raises many doubts. Although the approach of “Safety-by-Design” to the principles of drug development has helped in the assessment of the toxicity of nanomaterials, a combination of scientific efforts is constantly urgent to ensure the consistency of methods and processes. This will ensure that the quality of nanomaterials is controlled and their safe development is promoted. Safety issues are considered strategies for discovering novel toxicological-related mechanisms still needed to be promoted.

The use of nanomaterials in medicine depends largely on nanotoxicological evaluation in order to ensure safe application on living organisms. Artificial intelligence (AI) and machine learning (MI) can be used to analyze and interpret large amounts of data in the field of toxicology, such as data from toxicological databases and high-content image-based screening data. Physiologically based pharmacokinetic (PBPK) models and nano-quantitative structure–activity relationship (QSAR) models can be used to predict the behavior and toxic effects of nanomaterials, respectively. PBPK and Nano-QSAR are prominent ML tool for harmful event analysis that is used to understand the mechanisms by which chemical compounds can cause toxic effects, while toxicogenomics is the study of the genetic basis of toxic responses in living organisms. Despite the potential of these methods, there are still many challenges and uncertainties that need to be addressed in the field. In this review, we provide an overview of artificial intelligence (AI) and machine learning (ML) techniques in nanomedicine and nanotoxicology to better understand the potential toxic effects of these materials at the nanoscale.

Nanotechnology is an emerging technology that deals with nanosized particles possessing crucial research roles and application. Disciplines like chemistry, biology, physics, engineering, materials science, and health sciences provide an accumulated knowledge of nanotechnology. Nonetheless, it has vast submissions precisely in biology, electronics, and medicine. Aimed at drug delivery system, nanoparticles are based on the mechanism of entrapment of the drugs or biomolecules into the interior structure of the particles; another mechanism could be that the drugs or the biomolecules can be absorbed onto the exterior surfaces of the particles. Currently, nanoparticles (NPs) are used in the delivery of drugs, proteins, genes, vaccines, polypeptides, nucleic acids, etc. In recent years, various applications of the drug delivery system via NPs have encountered an enormous position sector like pharmaceutical, medical, biological, and others. Considering the impact of NPs in drug delivery systems, this review focuses on the detailed profile of NPs, its impact on biology and medicine, and their commercialization prospects.

The dire need for the assessment of human and environmental endangerments of nanoparticulate material has motivated the formulation of novel scientific tools and techniques to detect, quantify, and characterize these nanomaterials. Several of these paradigms possess enormous possibilities for applications in many of the realms of nanotoxicology. Furthermore, in a large number of cases, the limited capabilities to assess the environmental and human toxicological outcomes of customized and tailored multifunctional nanoparticles used for drug delivery have hindered their full exploitation in preclinical and clinical settings. With the ever-compounded availability of nanoparticulate materials in commercialized settings, an ever-arising popular debate has been egressing on whether the social, human, and environmental costs associated with the risks of nanomaterials outweigh their profits. Here we briefly review the various health, pharmaceutical, and regulatory aspects of nanotoxicology of engineered multifunctional nanoparticles in vitro and in vivo. Several aspects and issues encountered during the safety and toxicity assessments of these drug-delivery nanocarriers have also been summarized. Furthermore, recent trends implicated in the nanotoxicological evaluations of nanoparticulate matter in vitro and in vivo have also been discussed. Due to the absence of robust and rigid regulatory guidelines, researchers currently frequently encounter a larger number of challenges in the toxicology assessment of nanocarriers, which have also been briefly discussed here. Nanotoxicology has an appreciable and significant part in the clinical translational development as well as commercialization potential of nanocarriers; hence these aspects have also been touched upon. Finally, a brief overview has been provided regarding some of the nanocarrier-based medicines that are currently undergoing clinical trials, and some of those which have recently been commercialized and are available for patients. It is expected that this review will instigate an appreciable interest in the research community working in the arena of pharmaceutical drug development and nanoformulation-based drug delivery.

Cancer remains as the major cause of death worldwide. The main reason why available therapies fail is that a vicious cycle in established which initiates multiple pathways and recurrence after metastasis. Hyperthermic treatment, which involves heating tumor tissues to a moderate temperature of 40–43 °C, has emerged as an effective strategy for treating tumors. This method is highly efficient at destroying tumor cells and does not induce the side effects of conventional cancer treatments. On the other hand, hyperthermic treatment method can be co-administered with conventional treatments. Nanotechnology had created huge opportunities in almost all areas of research, including the field of hyperthermic treatment. The utilization of magnetic nanoparticles (MNPs) offers functionalities not possible using conventional magnetic materials. In this review, we detail recent developments and applications of MNPs for hyperthermic treatment and discuss future possibilities.

The universal presence of micro-nanoplastics (MNPLs) and its relative unknown effects on human health is a concern demanding reliable data to evaluate their safety. As ingestion is one of the main exposure routes for humans, we have assessed their hazard using two in vitro models that simulate the human intestinal barrier and its associated lymphoid system. Two different coculture models (differentiated Caco-2/HT29 intestinal cells and Caco-2/HT29 + Raji-B cells) were exposed to polystyrene nanoparticles (PSNPs) for 24 h. Endpoints such as viability, membrane integrity, NPS localization and translocation, ROS induction, and genotoxic damage were evaluated to have a comprehensive view of their potentially harmful effects. No significant cytotoxic effects were observed in any of the analyzed systems. In addition, no adverse effects were detected in the integrity or in the permeability of the barrier model. Nevertheless, confocal microscopy analysis showed that MNPLs were highly uptaken by both of the barrier model systems, and that translocation across the membrane occurred. Thus, MNPLs were detected into Raji-B cells, placed in the basolateral compartment of the insert. The internalization followed a dose-dependent pattern, as assessed by flow cytometry. Nonetheless, no genotoxic or oxidative DNA damage induction was detected in either case. Finally, no variations in the transcription of oxidative and stress genes could be detected in any of the in vitro barrier models. Our results show that MNPLs can enter and cross the epithelial barrier of the digestive system, as demonstrated when Raji-B cells were included in the model, but without exerting apparent hazardous effects.