Bioactivity of Engineered Nanoparticles

Nanoparticles (NPs) display unique physical and chemical properties to the toxicity of algae. Among the NPs, metal oxide NPs such as titanium dioxide (nano-TiO₂), zinc oxide (ZnO NPs), and copper oxide (CuO NPs) are the most used nanomaterials. Silver nanoparticles (Ag NPs), gold nanoparticles (Au NPs), and zero-valent iron nanoparticles (nZVI) have received considerable attention among noble metal materials. Besides, Quantum dots (QDs) and carbon-based nanoparticles are also common. To assess the ecological response of algae to NPs, we provide an overview of NPs ecotoxicological effects on algae from existing data and focus on the effect of different NPs on algae, the underlying mechanisms of NPs toxicity and their toxic effects on algae. Among the data available, NPs have been shown to exert from inhibitive to lethal effects on algae due to a high surface area, nanoscale size effects, and quantum effects.

The effects of engineered nanoparticles (ENPs) in living organisms are described in a myriad of articles. Most of the literature on this topic is devoted to plants of different gender and species. Studies from laboratories and greenhouse facilities highlight effects on chlorophyll production, plant growth, stress enzyme activities, phytotoxicity, cytotoxicity, and genotoxicity. With few exceptions, research reports show that toxic effects of ENPs on plants are associated with particle size, phase, surface properties, exposure concentration, and soil chemistry. ENPs have been found to be taken through roots from soilless/soil media and translocated to the aboveground organs. However, the uptake and translocation can occur in reverse if important amounts of ENPs are exposed to the foliage. This chapter includes an analysis of the most recent and relevant information about the interaction of ENPs with vascular plants. Most of the reviewed literature refers to highly produced and used ENPs. Data about exposure to carbon nanotubes (CNTs), cerium dioxide (nano-CeO₂), titanium dioxide (nano-TiO₂), zinc oxide (nano-ZnO), copper oxide (nano-CuO), gold (nano-Au), iron (nano-Fe₃O₄), silver (nano-Ag), and others ENPs are discussed.

Characteristics such as size, surface-to-volume ratio, and surface chemistry, among others, convey uniqueness to engineering nanoparticles (ENPs). The surface chemistry determines the stability and aggregation of ENPs and also constrains their applications, environmental fate, and interaction with living organisms. To avoid aggregation and improve stabilization, the surface chemistry of numerous ENPs has been modified through coating with several agents. However, the coating also changes their biointeractions. In this chapter we discuss literature concerning the uptake, translocation, accumulation, and physiological effects of surface-coated ENPs in economically important plants. We discussed existing information based on the type of ENP, coating agent, and species of plant. Negative and positive effects are discussed.

With the growing usage of nanoparticles (NPs) in industry, biomedicine, and daily life, an increasing chance for humans to be exposed to NPs has been issued. However, the basis of toxicity of most manufactured NPs is not fully understood. An important mechanism of nanotoxicity is reactive oxygen species (ROS) formation, which could cause oxidative stress, inflammation, and consequent cell death. NPs can interact with H₂O or O₂ in the physiological environment, resulting in the direct production of ROS, or affect the function of mitochondria and NADPH oxidase, resulting in the indirect production of ROS. ROS generation and oxidative stress were depicted by the hierarchical oxidative stress model. Critical determinants that can affect the generation of ROS, including NPs’ composition, size, shape, and surface chemistry, are briefly discussed in this review.

With the development and wide applications of engineered nanomaterials (ENMs), their impacts on human health have received increasing concerns. ENMs can enter human body through respiratory pathway, digestive tract, skin penetration, intravenous injection, and implantation, and then they are carried to distal organs via bloodstream and lymphatic functions to perturb physiological systems. It is very important to investigate the interactions between ENMs and biomolecules (the basic building blocks of the human body) such as phospholipid, protein, DNA, and some other small biological molecules. The chapter intends to discuss the chemical basis of interactions between ENMs and biomolecules, and the effects of the differences in surface morphology, composition, and modified groups of ENMs. The in-depth understanding of interactions between ENMs and biomolecules could lay foundations for further elucidating the effects of ENMs on human cells, organs, and physiological systems, which paves the way for human and environmental friendliness in the production and usage of ENMs.

Surface engineering facilitates incorporation of various bioactive compounds and provides unique advantages for the specific delivery of imaging and therapeutic agents. Several molecules with imaging, diagnostic, prognostic, sensing, and therapy can be incorporated in the bioformulations with the help of different surface engineering techniques. This chapter reviews drug carriers which were surface engineered for targeted drug delivery at the requisite location. A single or combination of surface engineering has been used for efficient delivery of carriers. The carriers reviewed here were divided into two categories: lipid-based carriers (liposomes and solid lipid nanoparticles) and non-lipid-based carriers (niosomes, polymeric nanoparticles, hydrogels, dendrimers, quantum dots, gold nanoparticles, and mesoporous silica nanoparticles). Various kinds of bioactive compounds along with the involvement of surface engineering techniques in incorporation were also discussed. This chapter focuses on recent advances in the surface engineering of nanocarriers for therapeutic applications.

Riboflavin receptors (RFRs) are overexpressed in several malignant cells, and have been characterized as an emerging tumor surface biomarker. In this article, we discuss the design principles of a RFR-targeted nanoparticle system and illustrate its applications with studies performed in our laboratories. This system is based on a poly(amidoamine) (PAMAM) dendritic polymer which is modified on the surface by conjugation with riboflavin (RF) as the targeting ligand. First, we discuss the application of this system for targeted drug delivery by its conjugation with methotrexate as an antitumor payload. In cell-based experiments performed in vitro, this drug conjugate displayed RF-dependent, potent inhibition of cell growth in RFR(+) KB carcinoma cells. Second, the use of the RF-conjugated dendrimer for gene delivery applications through the formation of polyplexes with plasmid DNA is described. The ability of this targeted system to significantly enhance gene transfection in epithelial cells points to its potential as a promising new class of nonviral vectors. Third, the tunability of the functional properties of the dendrimer through modular integration is illustrated with an optically active gold nanoparticle (AuNP). The resultant dendrimer-coated AuNPs have a unique capability for tumor cell imaging via surface plasmon resonance scattering. Finally, we discuss the biophysical basis of the multivalent mechanism involved in the tight and specific binding of a RF-conjugated multivalent dendrimer to RFRs on the cell surface. The design principles and proof of concept studies presented here are strongly supportive of the promising potential of RF-conjugated nanoparticles for delivery and imaging applications in tumors.

Recent advances in the development of novel nanomaterials and evaluation of their biomedical applications have shown promises of those multifunctional nanomaterials in the development of new approaches for cancer detection and therapy. The unique physicochemical properties of nanomaterials, small size, and large surface-area-to-volume ratio endow them with novel multifunctional capabilities for cancer imaging, drug delivery, and cancer therapy, referred to as theranostics, which are different from the traditional diagnosis and therapy approaches. To facilitate the translation of nanomaterials as imaging agents and drug delivery carriers into clinical applications, great efforts have been made on designing and improving biocompatibility, stability, safety, drug loading ability, targeted delivery, imaging signals, and thermal- or photodynamic responses. With the development of companion new imaging techniques and therapeutic approaches, several nanomaterials have demonstrated great theranostic potential in image-guided therapy of diseases, especially in cancer therapy. In this review, the current status and perspective of nanoparticles in the development of cancer theranostic agents will be discussed with a focus on several representative nanomaterials, including magnetic iron oxide nanoparticles, gold nanoparticles, silica nanoparticles, polymeric nanoparticles, and carbon nanomaterials.

Chemotherapy is one of the most conventionally used therapeutic interventions for treating various diseases. Chances of acquiring multidrug resistance in response to chemotherapeutic agents are exceedingly common among patients. Drug resistance arises mainly due to overexpression of efflux transporters such as P-glycoprotein and multidrug resistance-associated protein of the ATP-binding cassette superfamily of proteins, which significantly limits intracellular drug accumulation and drug activity. Although many approaches exist to overcome drug resistance, their uses are significantly limited in clinical practice. In this chapter, we demonstrate the superior functions of Pluronic-based technologies to overcome drug resistance. The present chapter highlights various aspects of Pluronic polymers, Pluronic conjugates, Pluronic nanotechnology, as well as their therapeutic implications for effective treatment strategies. We include the role of Pluronic polymers as a pharmaceutic excipient and drug delivery vehicle in this review. In addition, we highlight examples of Pluronic nanosystems that are currently in preclinical development, clinical trials, and clinically translatable formulations. Furthermore, a number of innovative Pluronic nano-designs of advanced therapeutics for future medicinal applications are presented. Collectively, the use of Pluronic-based nanoformulations discussed in this chapter suggests sensitization and prevention of drug resistance. Such an approach not only minimizes the dose required for treatment, but also minimizes the number of treatment cycles, which is useful in a clinical scenario.

In recent years, there has been growing interest in the existence of natural nanoparticles in the environment and their subsequent influence to the ecological health. This chapter presents the current status on thermally- and light-induced formation of silver nanoparticles (AgNPs) under environmentally relevant conditions. Influenced environmental parameters include temperature, pH, oxic/anoxic environment, and concentrations of precursors Ag⁺ ions and natural organic matter (NOM). Surface-catalyzed reduction of Ag⁺ could describe the formation of AgNPs under various conditions. The redox species of iron (Fe(II)/Fe(III)) in the thermally induced processes enhanced the formation of AgNPs. Moieties of NOM, Ag–NOM complexes, and reactive oxygen species, ROS (e.g., \( {{\text{O}}_{2}}^{\cdot - } \)) were provoked to explain the formation of AgNPs. Stability studies on formed AgNPs from Ag(I)–NOM reaction mixtures have shown their stability for days to several months. However, cations of the natural waters such as Na⁺, K⁺, Mg²⁺, and Ca²⁺ can destabilize the AgNPs. A preliminary investigation on the toxicity of AgNPs, formed in the mixture of Ag⁺-humic acid, suggests that lower minimum inhibition concentration against Gram-negative bacteria and Gram-positive bacteria compared to engineered AgNPs.

We studied purposefully produced silver, gold, iron oxide, copper oxide, nickel oxide, manganese oxide, lead oxide, and zinc oxide nanoparticles using two experimental models: (a) a single intratracheal (IT) instillation in low doses 24 h before the bronchoalveolar lavage to obtain a fluid for cytological and biochemical assessment; (b) repeated intraperitoneal (IP) injections during 6–7 weeks in non-lethal doses to assess the thus induced subchronic intoxication by a lot of functional and morphological indices and by the distribution and elimination of respective nanoparticles. Along with assessing the toxicity of these metallic nanoparticles (Me-NPs) acting separately, we also studied the same effects of some practically relevant Me-NP combinations. Besides, we carried out a 10-month inhalation experiment with an iron oxide (Fe₂O₃) nano-aerosol. We demonstrated that Me-NPs are much more noxious as compared with their fine micrometric counterparts although physiological mechanisms of their elimination from lungs proved highly active. At the same time, the in situ cytotoxicity, organ-systemic toxicity and in vivo genotoxicity of Me-NPs having a given geometry strongly depends on their chemical nature as well as on the specific mechanisms of action characteristic of a given metal. Even though being water-insoluble, Me-NPs are significantly solubilized in some biological milieus, and this process plays an important part in their biokinetics in vivo. In toto, Me-NPs are one of the most dangerous occupational and environmental hazards due to their cytotoxicity and genotoxicity, and therefore standards or recommended values of presumably safe Me-NP concentrations in the workplace and ambient air should be significantly lower as compared with those established for their micrometric counterparts. At the same time, the toxicity and even genotoxicity of Me-NPs can be significantly attenuated by background or preliminary administration of adequately composed combinations of some bioactive agents in innocuous doses.

The production, usage, and disposal of engineered nanomaterial (ENM)-based products inevitably increased their environmental accumulation and human exposures. Liver is the major organ for deposition of ENMs after their clearance from the circulation system. Accumulation of ENMs in liver may cause hepatic oxidative stress, inflammation, DNA damage, hepatocyte death, as well as liver fibrosis in healthy populations. In subpopulations with various liver diseases, such effects may be aggravated. Critical factors such as properties of ENMs, animal experimental protocols, and status of liver are discussed, as well as possible future directions.

Silicon quantum dots (Si QDs) represent a special class of nanomaterials with distinctive properties, being used in different applications such as photovoltaics, optoelectronics devices, and biomedical ones. They have excellent luminescence at UV irradiation, tunable band gap, and resistance against photobleaching compared to standard dyes. Being less toxic in comparison with conventional metal-containing QDs, they received growing research interest in the last decade as a more biocompatible alternative to which displayed toxicological concerns. There are several physical and chemical methods for Si QDs synthesis, each of them involving advantages and disadvantages. In physical methods, the experimental setup is very simple and parameters can be adjusted from outside in order to obtain the desired size of nanoparticles. Chemical methods seem to be attractive due to the huge scale of productions, but the purity control of the material and experimental setup are more complicated. For biomedical applications, many techniques have been established to achieve water-soluble Si QDs and for their conjugation with biomolecules that render them to specific biological targets. Si QDs have become powerful nanomaterials in various biomedical applications, a promising approach for in vivo imaging, tumor biology investigation, and cancer treatment. Besides of all these advantages, their characteristics can also trigger cytotoxicity in healthy cells by different mechanisms that have been in vitro and in vivo investigated in the last years. This chapter summarizes the major methods of synthesis and recent advances in bioconjugation strategies for preparing high-quality Si QDs, with a focus on their toxicity evaluation and bioapplications.

In this chapter, we discuss the development and application of molecular modeling methods to analyze and forecast the experimental properties of nanomaterials. We mainly focus on Quantitative Nanostructure—Activity Relationships (QNAR) to evaluate the extent of biological activities potentially induced by various types of nanomaterials. First, we present the basic principles of QNAR modeling that uses machine-learning techniques to establish quantified links between the biological endpoint of interest (e.g., cytotoxicity, cell death, ROS production) and nanomaterials’ characteristics. Second, we briefly review recently published studies reporting on the QNAR modeling of the largest and most significant datasets of nanomaterials available in the public domain. Third, we discuss some perspectives for the use of molecular modeling on nanomaterials. Overall, we show how molecular modeling can represent a key element for enabling the rational design of nanomaterials with the desired activity and safety profile.