Nanoparticles: tech trends in healthcare

Nanotechnology is the use of matter on an atomic, molecular, and supramolecular scale for various purposes. Nanotechnology field of application is very much diverse which includes surface science, organic chemistry, molecular biology, semiconductor physics, energy storage, engineering, microfabrication, and molecular engineering. Its medical application ranges from biological devices, nano-electronic biosensors, and to future biological machines. The main issue nowadays for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials. Lot more functionalities can be added to nanomaterials by interfacing them with biological structures. The size of nanomaterials is similar most biological molecules and so useful for both in vivo and in vitro biomedical research and applications. The integration of nanomaterials with biology had paved path to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications and drug delivery vehicles.

Targeted drug delivery vehicles mediated by nanocarriers and aptamers for posterior eye disease therapeutics: barriers, recent advances and potential opportunities

Nanomedicine and aptamer have excellent potential in giving play to passive and active targeting respectively, which are considered to be effective strategies in the retro-ocular drug delivery system. The presence of closely adjoined tissue structures in the eye makes it difficult to administer the drug in the posterior segment of the eye. The application of nanomedicine could represent a new avenue for the treatment, since it could improve penetration, achieve targeted release, and improve bioavailability. Additionally, a novel type of targeted molecule aptamer with identical objective was proposed. As an emerging molecule, aptamer shows the advantages of penetration, non-toxicity, and high biocompatibility, which make it suitable for ocular drug administration. The purpose of this paper is to summarize the recent studies on the effectiveness of nanoparticles as a drug delivery to the posterior segment of the eye. This paper also creatively looks forward to the possibility of the combined application of nanocarriers and aptamers as a new method of targeted drug delivery system in the field of post-ophthalmic therapy.

Perturbation of Cellular Redox Homeostasis Dictates Divergent Effects of Polybutyl Cyanoacrylate (PBCA) Nanoparticles on Autophagy

Nanoparticles (NPs) are used in our everyday life, including as drug delivery vehicles. However, the effects of NPs at the cellular level and their impacts on autophagy are poorly understood. Here, we demonstrate that the NP drug delivery vehicle poly(butyl cyanoacrylate) (PBCA) perturbs redox homeostasis in human epithelial cells, and that the degree of redox perturbation dictates divergent effects of PBCA on autophagy. Specifically, PBCA promoted functional autophagy at low concentrations, whereas it inhibited autophagy at high concentrations. Both effects were completely abolished by the antioxidant N-acetyl cysteine (NAC). High concentrations of PBCA inhibited MAP1LC3B/GABARAP lipidation and LC3 flux, and blocked bulk autophagic cargo flux induced by mTOR inhibition. These effects were mimicked by the redox regulator H2O2. In contrast, low concentrations of PBCA enhanced bulk autophagic cargo flux in a Vps34-, ULK1/2- and ATG13-dependent manner, yet interestingly, without an accompanying increase in LC3 lipidation or flux. PBCA activated MAP kinase signaling cascades in a redox-dependent manner, and interference with individual signaling components revealed that the autophagy-stimulating effect of PBCA required the action of the JNK and p38–MK2 pathways, whose activities converged on the pro-autophagic protein Beclin-1. Collectively, our results reveal that PBCA exerts a dual effect on autophagy depending on the severity of the NP insult and the resulting perturbation of redox homeostasis. Such a dual autophagy-modifying effect may be of general relevance for redox-perturbing NPs and have important implications in nanomedicine.

Citrate-capped gold nanoparticles with a diameter of 14nm alter the expression of genes associated with stress response, cytoprotection and lipid metabolism in CaCo-2 cells

Advancements in nanotechnology have provided insight into the unique opportunities for the application of nanomaterials such as gold nanoparticles (AuNPs) in medicine due to their remarkable properties, which includes low toxicity, large surface area, and the ease of synthesis and conjugation to other molecules. Therefore, AuNPs are often preferred for bio-applications. Citrate-capped AuNPs (cAuNPs) have been reported to be non-cytotoxic and are used in numerous studies as drug delivery vehicles to treat various diseases. However, the limitations of bioassays often used to assess the toxicity of AuNPs have been well documented. Herein, we investigate the cytotoxicity of 14nm cAuNPs in the human colorectal adenocarcinoma (Caco-2) cell line. Treatment conditions (i.e., dose and exposure time) that were established to be non-toxic to Caco-2 cells were used to investigate the effect of cAuNPs on the expression of a Qiagen panel of 86 genes involved in cytotoxicity. Out of 86 studied, 23 genes were differentially expressed. Genes involved in oxidative stress and antioxidant response, endoplasmic reticulum (ER) stress and unfolded protein response (UPR), heat shock response (HSR), and lipid metabolism were more affected than others. While low concentrations of 14nm cAuNPs was not cytotoxic and did not cause cell death, cells treated with these nanoparticles experienced ER and oxidative stress, resulting in the activation of cytoprotective cellular processes. Additionally, several genes involved in lipid metabolism were also affected. Therefore, 14nm cAuNPs can safely be used as drug delivery vehicles at low doses.

Recent Advancements in Serum Albumin-Based Nanovehicles Toward Potential Cancer Diagnosis and Therapy

Recently, drug delivery vehicles based on nanotechnology have significantly attracted the attention of researchers in the field of nanomedicine since they can achieve ideal drug release and biodistribution. Among the various organic or inorganic materials that used to prepare drug delivery vehicles for effective cancer treatment, serum albumin-based nanovehicles have been widely developed and investigated due to their prominent superiorities, including good biocompatibility, high stability, nontoxicity, non-immunogenicity, easy preparation, and functionalization, allowing them to be promising candidates for cancer diagnosis and therapy. This article reviews the recent advances on the applications of serum albumin-based nanovehicles in cancer diagnosis and therapy. We first introduce the essential information of bovine serum albumin (BSA) and human serum albumin (HSA), and discuss their drug loading strategies. We then discuss the different types of serum albumin-based nanovehicles including albumin nanoparticles, surface-functionalized albumin nanoparticles, and albumin nanocomplexes. Moreover, after briefly discussing the application of serum albumin-based nanovehicles used as the nanoprobes in cancer diagnosis, we also describe the serum albumin-based nanovehicle-assisted cancer theranostics, involving gas therapy, chemodynamic therapy (CDT), phototherapy (PTT/PDT), sonodynamic therapy (SDT), and other therapies as well as cancer imaging. Numerous studies cited in our review show that serum albumin-based nanovehicles possess a great potential in cancer diagnostic and therapeutic applications.

Trehalose glycolipids as immunomodulators and their incorporation into liposomes for drug delivery

<p>The development of novel therapies for cancer and other diseases is an area of enormous research effort due to the growing need for better patient outcomes. As such, not only is the chemical synthesis of new drugs and adjuvants required, but ways to improve drug delivery also need to be explored. Accordingly, there has been much recent effort towards the synthesis and the biological evaluation of bacterial cell wall components as immunomodulatory compounds. To this end, trehalose glycolipids (TGs), which have been isolated from bacteria of the Mycobacteria family, are of significant interest, due to their anti-tumour and adjuvant activities. In this thesis, the efficient synthesis of trehalose monoesters (TMEs) was investigated and the ability of these monoesters to activate macrophages via Mincle was studied and compared to the activities of their trehalose diester (TDE) counterparts. In this way, a better understanding of how TG structure influences biological activity was explored. Liposomes containing a representative TG (the C26 TDE) were also synthesised, with the objective being to explore whether TGliposomes could be used as improved drug delivery vehicles. To meet these overall objectives, TGs in solution, as well as TG incorporated into liposomes, were tested for their ability to activate macrophages derived from both C57BL/6 and Mincle-/- mice, whereby the Mincle receptor is a known receptor for TDEs. In the TME studies, an optimised synthesis of the monoesters was developed. The ability of the TMEs to active macrophages was explored and, for the first time, it was observed that TMEs have similar biological activities to TDEs. In the TGliposome studies, a variety of liposomes containing different concentrations of phosphatidylcholine (PC) as well as the C26 TDE was prepared, so as to explore how differences in these two constituent parts influence the activation of macrophages. From this work, it was observed that increasing concentrations of TG in the liposome and increasing concentrations of liposomes gave increased macrophage activation. A concentration of PC above 200 !M also led to macrophage activation, and non-specific cell death was observed at time points > 48 h (for the wild type macrophages) and at time points ≥ 48 h for the Mincle-/- macrophages. Thus, in the case of the TG liposomes, macrophage activation is independent of Mincle, which was unusual as macrophage activation in the case of the individual TGs was dependent on this receptor. Taken as a whole, these results pave the way for further investigations into utilising TGs in the treatment of diseases. In particular, this work provided insight into the requirement of TG/Mincle binding for improved TGs as potential adjuvants. Moreover, these studies demonstrated that the incorporation of TGs into liposomes leads to enhanced macrophage activation and therefore, potentially enhanced phagocytosis by these immune cells. Accordingly, TG-liposomes may find future application as drug delivery vehicles, in diseases where macrophages play a prominent role.</p>