Biomolecular Corona Dictates Aβ Fibrillation Process

Amyloid beta (Aβ), which forms toxic oligomers and fibrils in brain tissues of patients with Alzheimer's disease, is broadly used as a model protein to probe the effect of nanoparticles (NPs) on oligomerization and fibrillation process. However, majority of the reports in the field, ignored the effect of biomolecular corona on the fibrillogenesis of the Aβ proteins. Biomolecular corona, which is a layer composed of various types of biomolecules that covers surface of NPs upon their interaction with biological fluids, determines the biological fates of NPs. Therefore, during in vivo interaction of NPs with Aβ protein, what the Aβ actually "sees" is the human plasma- and/or cerebrospinal fluid (CSF)-biomolecular coated NPs rather than the pristine surface of NPs. Here, to mimic the in vivo effects of therapeutic NPs as anti-fibrillation agents, we probed the effects of biomolecular corona derived from human CSF and/or plasma on Aβ fibrillation. The results demonstrated that the type of biomolecular corona can dictate the inhibitory or acceleratory effect of NPs on Aβ1-42 and Aβ25-35 fibrillation processes. More specifically, we found that the plasma biomolecular corona coated gold NPs, with sphere and rod shapes, has less inhibitory effects on Aβ1-42 fibrillation kinetics compared to CSF biomolecular corona coated- and pristine- NPs. Opposite results obtained for Aβ25-35 peptide, where the pristine NPs accelerated the Aβ25-35 fibrillation process while corona-coated ones demonstrated an inhibitory effect. In addition, the CSF biomolecular corona had less inhibitory effects than those obtained from plasma. © 2018 American Chemical Society

Magnetic nanocatalysts as multifunctional platforms in cancer therapy through the synthesis of anticancer drugs and facilitated Fenton reaction

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed. Key Scientific Concepts of Review: This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.Scopu

Amyloid fibril inhibition, acceleration, or fragmentation; Are nano-based approaches advance in the right direction?

Nanotechnology-based approaches have shown promising potential to overcome the challenges associated with current therapeutic/diagnostic approaches and offer exciting solutions to improve the quality of life of Alzheimer's Disease (AD) patients. Unfortunately, thus far they have failed in clinical translation. These disappointing results question whether nanotechnology-based therapeutic strategies are heading in the right direction. Here, we re-consider the problems and current therapeutic approaches from new angles and suggest what might have been overlooked in advanced AD therapy

Impact of plasma concentration of transferrin on targeting capacity of nanoparticles

It is becoming increasingly accepted that various diseases have a capacity to alter the composition of plasma proteins. This alteration in protein composition may consequently change the targeting capacity of nanoparticles (NPs). In this study, the impact of a model targeting ligand's (i.e., Transferrin; Tf) concentration in human plasma on the targeting capacity of gold NPs (Au NPs), pre-conjugated with Tf, is investigated. Our findings demonstrate that the protein corona formation by both healthy and Tf depleted human plasma diminishes the targeting efficacy of Au NPs within human cancer cells despite a preservation of targeting ability by plasma with excess Tf (10-fold). Moreover, the plasma samples obtained from patients with various Tf levels (e.g., thalassemia major, sickle cell anemia, aplastic anemia, and iron deficiency anemia) have affected the accessibility of the targeting Tf in the corona layer and subsequently affected their targeting ability, which emphasizes the critical role of disease-specific protein corona on the efficacy of Au NPs. Ultimately, variations of protein concentration (e.g., due to disease occurrence and progress) in plasma affect its recruiting in corona formation, and in turn, affect the targeting and therapeutic efficacies of Au NPs. © The Royal Society of Chemistry 2020

Nanozyme-based sensing platforms for detection of toxic mercury ions: An alternative approach to conventional methods

Mercury (Hg) is known as a poisonous heavy metal which stimulates a wide range of adverse effects on the human health. Therefore, development of some feasible, practical and highly sensitive platforms would be desirable in determination of Hg2+ level as low as nmol L?1 or pmol L?1. Different approaches such as ICP-MS, AAS/AES, and nanomaterial-based nanobiosensors have been manipulated for determination of Hg2+ level. However, these approaches suffer from expensive instruments and complicated sample preparation. Recently, nanozymes have been assembled to address some disadvantages of conventional methods in the detection of Hg2+. Along with the outstanding progress in nanotechnology and computational approaches, pronounced improvement has been attained in the field of nanozymes, recently. To accentuate these progresses, this review presents an overview on the different reports of Hg2+-induced toxicity on the different tissues followed by various conventional approaches validated for the determination of Hg2+ level. Afterwards, different types of nanozymes like AuNPs, PtNPs for quantitative detection of Hg2+ were surveyed. Finally, the current challenges and the future directions were explored to alleviate the limitation of nanozyme-based platforms with potential engineering in detection of heavy metals, namely Hg2+. The current overview can provide outstanding information to develop nano-based platforms for improvement of LOD and LOQ of analytical methods in sensitive detection of Hg2+ and other heavy metals.Scopu

3D bioprinting of engineered breast cancer constructs for personalized and targeted cancer therapy

The bioprinting technique with specialized tissue production allows the study of biological, physiological, and behavioral changes of cancerous and non-cancerous tissues in response to pharmacological compounds in personalized medicine. To this end, to evaluate the efficacy of anticancer drugs before entering the clinical setting, tissue engineered 3D scaffolds containing breast cancer and derived from the especially patient, similar to the original tissue architecture, can potentially be used. Despite recent advances in the manufacturing of 3D bioprinted breast cancer tissue (BCT), many studies still suffer from reproducibility primarily because of the uncertainty of the materials used in the scaffolds and lack of printing methods. In this review, we present an overview of the breast cancer environment to optimize personalized treatment by examining and identifying the physiological and biological factors that mimic BCT. We also surveyed the materials and techniques related to 3D bioprinting, i.e, 3D bioprinting systems, current strategies for fabrication of 3D bioprinting tissues, cell adhesion and migration in 3D bioprinted BCT, and 3D bioprinted breast cancer metastasis models. Finally, we emphasized on the prospective future applications of 3D bioprinted cancer models for rapid and accurate drug screening in breast cancer.Scopu

Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.Scopu

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health. Communicated by Ramaswamy H. Sarma.Scopu

Silybin as a potent inhibitor of a-synuclein aggregation and associated cytotoxicity against neuroblastoma cells induced by zinc oxide nanoparticles

a-synuclein (a-syn) amyloid fibrils, the leading neurotoxic types, are predominately formed through interaction with nanoparticles (NPs). However, some natural compounds like silybin can reduce the formation of NPs-induced amyloid fibrils and related cytotoxicity. Herein, we assayed the ZnO-induced a-syn amyloid fibril formation and underlying cytotoxicity in the absence and presence of silybin using a wide range of multispectroscopic (ThT fluorescence, Congo red absorbance, and CD), TEM, and cellular (MTT, LDH, ROS, and caspase-3) approaches. Spectroscopy data and TEM investigation showed that ZnO NPs accelerate the induction of a-syn amyloid fibrils in the amyloidogenic conditions. However, silybin as a bioactive compound can result in inhibition of a-syn fibrillogenesis induced by ZnO NPs. The potent inhibitory impact of silybin on cytotoxicity of a-syn amyloid fibrils induced by ZnO NPs was also assessed by cellular assays. It was depicted that the mortality, LDH release, ROS production, and caspase-3 activity upon addition of silybin were less than those reported in absence of this small molecule. These outcomes revealed that silybin is of great importance as neuroprotective and therapeutic small molecules for NP-induced protein aggregation and related cytotoxicity.Scopu

Irreversible thermal inactivation and conformational lock of alpha glucosidase

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of �-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using p-nitrophenyl �-d-glucopyranoside (pNPG) as the synthetic substrate following absorbance at 410 nm by UV?Vis spectrophotometer. The interface structure and residual activity plot were analyzed via biochemical measurements by means of conformational lock theory, as well. The thermal inactivation curves were plotted in temperature interval from 30 to 50 �C. Based on experimental and structural data we suggested intermediates during inactivation before the loss of enzyme activity. Arrhenius plot for thermal inactivation rate constant showed biphasic appearance related to before and after 45�C temperature. The contact areas between two subunits were ruptured and unlocked stepwise during dimer dissociation. Cleavage of these areas induced the dissociation of the subunits along with destruction of the active centers and subsequently the loss of activity. It seems that the contact areas interact with active centers by conformational changes involving secondary structural elements.Scopu