A critical review of the current knowledge regarding the biological impact of nanocellulose.

Several forms of nanocellulose, notably cellulose nanocrystals and nanofibrillated cellulose, exhibit attractive property matrices and are potentially useful for a large number of industrial applications. These include the paper and cardboard industry, use as reinforcing filler in polymer composites, basis for low-density foams, additive in adhesives and paints, as well as a wide variety of food, hygiene, cosmetic, and medical products. Although the commercial exploitation of nanocellulose has already commenced, little is known as to the potential biological impact of nanocellulose, particularly in its raw form. This review provides a comprehensive and critical review of the current state of knowledge of nanocellulose in this format. Overall, the data seems to suggest that when investigated under realistic doses and exposure scenarios, nanocellulose has a limited associated toxic potential, albeit certain forms of nanocellulose can be associated with more hazardous biological behavior due to their specific physical characteristics.

Decoupling the shape parameter to assess gold nanorod uptake by mammalian cells.

The impact of nanoparticles (NPs) upon biological systems can be fundamentally associated with their physicochemical parameters. A further often-stated tenet is the importance of NP shape on rates of endocytosis. However, given the convoluted parameters concerning the NP-cell interaction, it is experimentally challenging to attribute any findings to shape alone. Herein we demonstrate that shape, below a certain limit, which is specific to nanomedicine, is not important for the endocytosis of spherocylinders by either epithelial or macrophage cells in vitro. Through a systematic approach, we reshaped a single batch of gold nanorods into different aspect ratios resulting in near-spheres and studied their cytotoxicity, (pro-)inflammatory status, and endocytosis/exocytosis. It was found that on a length scale of ∼10-90 nm and at aspect ratios less than 5, NP shape has little impact upon their entry into either macrophages or epithelial cells. Conversely, nanorods with an aspect ratio above 5 were preferentially endocytosed by epithelial cells, whereas there was a lack of shape dependent uptake following exposure to macrophages in vitro. These findings have implications both in the understanding of nanoparticle reshaping mechanisms, as well as in the future rational design of nanomaterials for biomedical applications.

Synthesis, characterization, antibacterial activity and cytotoxicity of hollow TiO2-coated CeO2 nanocontainers encapsulating silver nanoparticles for controlled silver release.

Biomaterials as implants are being applied more extensively in medicine due to their on-going development and associated improvements, and the increase in human life expectancy. Nonetheless, biomaterial-related infections, as well as propagating bacterial resistance, remain significant issues. Therefore, there is a growing interest for silver-based drugs because of their efficient and broad-range antimicrobial activity and low toxicity to humans. Most newly-developed silver-based drugs have an extremely fast silver-ion release, increasing adverse biological impact to the surrounding tissue and achieving only short-term antimicrobial activity. Nanoencapsulation of these drugs is hypothesized as beneficial for controlling silver release, and thus is the aim of the present study. Initially, an amorphous or crystalline (anatase) titania (TiO2) coating was synthesized around silver nanoparticle-containing (AgNP) ceria (CeO2) nanocontainers using a sonication method forming AgNP/CeO2/TiO2 nanocontainers. These nanocontainers were characterized by high-resolution transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, gas sorption experiments and energy-dispersive X-ray spectroscopy. Silver release, monitored by using inductively coupled plasma optical emission spectroscopy, showed that these containers prevented silver release in water at neutral pH, and released the silver in concentrated nitric acid solution (pH = 1.1). The AgNP/CeO2/TiO2 nanocontainers showed an antibacterial activity against E. coli, however a concentration-dependent cytotoxicity towards a model epithelial barrier cell type (A549 cells) was observed. These nanocontainers offer the concept of potentially controlling silver delivery for the prevention of implant-associated infections.

Integrating silver compounds and nanoparticles into ceria nanocontainers for antimicrobial applications.

Silver compounds and nanoparticles (NPs) are gaining increasing interest in medical applications, specifically in the treatment and prevention of biomaterial-related infections. However, the silver release from these materials, resulting in a limited antimicrobial activity, is often difficult to control. In this paper, ceria nanocontainers were synthesized by a template-assisted method and were then used to encapsulate silver nitrate (AgNO3/CeO2 nanocontainers). Over the first 30 days, a significant level of silver was released, as determined using inductively coupled plasma optical emission spectroscopy (ICP-OES). A novel type of ceria container containing silver NPs (AgNP/CeO2 containers) was also developed using two different template removal methods. The presence of AgNPs was confirmed both on the surface and in the interior of the ceria containers by X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Upon removal of the template by calcination, the silver was released over a period exceeding three months (>90 days). However, when the template was removed by dissolution, the silver release was shortened to ≤14 days. The antimicrobial activity of the silver-containing CeO2 containers was observed and the minimum bactericidal concentration (MBC) was determined using the broth dilution method. Investigation on human cells, using a model epithelial barrier cell type (A549 cells), highlighted that all three samples induced a heightened cytotoxicity leading to cell death when exposed to all containers in their raw form. This was attributed to the surface roughness of the CeO2 nanocontainers and the kinetics of the silver release from the AgNO3/CeO2 and AgNP/CeO2 nanocontainers. In conclusion, despite the need for further emphasis on their biocompatibility, the concept of the AgNP/CeO2 nanocontainers offers a potentially alternative long-term antibactericidal strategy for implant materials.

Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity.

After the health catastrophe resulting from the widespread use of asbestos which was once hailed as a new miracle material, the increasing use of carbon nanotubes (CNTs) has spawned major concern due to their similarities in terms of size, shape and poor solubility. Assessment of genotoxicity has shown that CNTs can damage DNA in vitro and in vivo. The genotoxic potential of different CNT samples varies considerably, however, with negative findings reported in a number of studies, probably due to the enormous heterogeneity of CNTs. The observed spectrum of genotoxic effects shows similarities with those reported for asbestos fibres. Mutagenicity has been found in vivo but in bacterial assays both asbestos and CNTs have mostly tested negative. An overview of key experimental observations on CNT-induced genotoxicity is presented in the first half of this review. In the second part, the potential mechanisms of CNT-elicited genotoxicity are discussed. Whereas CNTs possess intrinsic ROS-scavenging properties they are capable of generating intracellular ROS upon interaction with cellular components, and can cause antioxidant depletion. These effects have been attributed to their Fenton-reactive metals content. In addition, CNTs can impair the functionality of the mitotic apparatus. A noteworthy feature is that frustrated phagocytosis, which is involved in asbestos-induced pathology, has been observed for specific CNTs as well. The involvement of other mechanisms generally implicated in particle toxicity, such as phagocyte activation and impairment of DNA repair, is largely unknown at present and needs further investigation.