Nanocarrier design-function relationship: The prodigious role of properties in regulating biocompatibility for drug delivery applications.

The concept of drug delivery systems as a magic bullet for the delivery of bioactive compounds has emerged as a promising approach in the treatment of different diseases with significant advantages over the limitations of traditional methods. While nanocarrier-based drug delivery systems are the main advocates of drug uptake because they offer several advantages including reduced non-specific biodistribution, improved accumulation, and enhanced therapeutic efficiency; their safety and biocompatibility within cellular/tissue systems are therefore important for achieving the desired effect. The underlying power of "design-interplay chemistry" in modulating the properties and biocompatibility at the nanoscale level will direct the interaction with their immediate surrounding. Apart from improving the existing nanoparticle physicochemical properties, the balancing of the hosts' blood components interaction holds the prospect of conferring newer functions altogether. So far, this concept has been remarkable in achieving many fascinating feats in addressing many challenges in nanomedicine such as immune responses, inflammation, biospecific targeting and treatment, and so on. This review, therefore, provides a diverse account of the recent advances in the fabrication of biocompatible nano-drug delivery platforms for chemotherapeutic applications, as well as combination therapy, theragnostic, and other diseases that are of interest to scientists in the pharmaceutical industries. Thus, careful consideration of the "property of choice" would be an ideal way to realize specific functions from a set of delivery platforms. Looking ahead, there is an enormous prospect for nanoparticle properties in regulating biocompatibility.

Advancements in electrochemical technologies for the removal of fluoroquinolone antibiotics in wastewater: A review.

In recent times, the need to make water safer and cleaner through the elimination of recalcitrant pharmaceutical residues has been the aim of many studies. Fluoroquinolone antibiotics such as ciprofloxacin, norfloxacin, enrofloxacin, and levofloxacin are among the commonly detected pharmaceuticals in wastewater. Since the presence of these pharmaceuticals in water bodies poses serious risks to living organisms, it is vital to adopt effective wastewater treatment techniques for their complete removal. Electrochemical technologies such as photoelectrocatalysis, electro-Fenton, electrocoagulation, and electrochemical oxidation have been established as techniques capable of the complete removal of organics including pharmaceuticals from wastewater. Hence, this review presents discussions on the recent progress (literature within 2018-2022) in the applications of common electrochemical processes for the degradation of fluoroquinolone antibiotics from wastewater. The fundamentals of these processes are highlighted while the results obtained using the processes are critically discussed. Furthermore, the inherent advantages and limitations of these processes in the mineralization of fluoroquinolone antibiotics are clearly emphasized. Additionally, appropriate recommendations are made toward improving electrochemical technologies for the complete removal of these pharmaceuticals with minimal energy consumption. Therefore, this review will serve as a bedrock for future researchers concerned with wastewater treatments to make informed decisions in the selection of suitable electrochemical techniques for the removal of pharmaceuticals from wastewater.

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System.

Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.

Bimetallic Au@Pd nanodendrite system incorporating multimodal intracellular imaging for improved doxorubicin antitumor efficiency.

The sufficient accumulation of drugs is crucial for efficient treatment in a complex tumor microenvironment. Drug delivery systems (DDS) with high surface area and selective cytotoxicity present a novel approach to mitigate insufficient drug loading for improved therapeutic response. Herein, a doxorubicin-conjugated bimetallic gold-core palladium-shell nanocarrier with multiple dense arrays of branches (Au@PdNDs.PEG/DOX) was characterized and its efficacy against breast adenocarcinoma (MCF-7) and lung adenocarcinoma (A549) cells were evaluated. Enhanced darkfield and hyperspectral imaging (HSI) microscopy were used to study the intracellular uptake and accumulation of the DOX-loaded nanodendrites A fascinating data from a 3D-CytoViva fluorescence imaging technique provided information about the dynamics of localization and distribution of the nanocarrier. In vitro cytotoxicity assays indicated that Au@PdNDs.PEG/DOX inhibited the proliferative effects of MCF-7 cells at equivalent IC50 dosage compared to DOX alone. The nanocarrier triggered higher induction of apoptosis proved by a time-dependent phosphatidylserine V release, cell cycle arrest, and flow cytometry analysis. Moreover, the cell cycle phase proportion increase suggests that the enhanced apoptotic effect induced by Au@PdNDs.PEG/DOX was via a G2/M phase arrest. Thus, this study demonstrated the potential of dendritic nanoparticles to improve DOX therapeutic efficiency and plasmonic-mediated intracellular imaging as a suitable theranostic platform for deployment in nanomedicine.

Exercise, CaMKII, and type 2 diabetes.

Individuals who exercise regularly are protected from type 2 diabetes and other metabolic syndromes, in part by enhanced gene transcription and induction of many signaling pathways crucial in correcting impaired metabolic pathways associated with a sedentary lifestyle. Exercise activates Calmodulin-dependent protein kinase (CaMK)II, resulting in increased mitochondrial oxidative capacity and glucose transport. CaMKII regulates many health beneficial cellular functions in individuals who exercise compared with those who do not exercise. The role of exercise in the regulation of carbohydrate, lipid metabolism, and insulin signaling pathways are explained at the onset. Followed by the role of exercise in the regulation of glucose transporter (GLUT)4 expression and mitochondrial biogenesis are explained. Next, the main functions of Calmodulin-dependent protein kinase and the mechanism to activate it are illustrated, finally, an overview of the role of CaMKII in regulating GLUT4 expression, mitochondrial biogenesis, and histone modification are discussed.

The stimuli-responsive properties of doxorubicin adsorbed onto bimetallic Au@Pd nanodendrites and its potential application as drug delivery platform.

HYPOTHESIS: Bimetallic nanoparticles have continued to attract interest as drug delivery systems in cancer therapy even though their nature of interaction with small molecules is limited. Currently, many delivery systems based on monometallic nanoparticles are being fabricated for loading of drugs, thus prompting the need to explore and get more understanding of dendritic bimetallic nanostructure-drug interaction. EXPERIMENTS: The bimetallic gold-core palladium-dendritic shell nanoparticles (Au@PdNDs) were synthesized by hot injection method and stabilized with methoxy polyethylene glycol thiol (mPEG-SH). An anti-cancer drug, doxorubicin (DOX) was conjugated to the bimetallic nanodendrites leading to the formation of DOX/Au@PdNDs.PEG complex. We used TEM, FTIR, and zeta-potential to study the drug-nanodendrites interaction. The effect of DOX binding and release capacity with regards to pH, adsorption kinetics, solvent polarity, isotherms and temperature on Au@PdNDs.PEG were investigated. FINDINGS: The results showed a spontaneous heterogeneous binding of DOX on the Au@PdNDs.PEG surfaces and time-dependent loading capacity of ~90% maximum adsorption within 24 h. Moreover, the experimental results showed that the adsorption isotherm data fitted well with the Freundlich model and a pseudo-second order adsorption kinetics. The desorption of DOX was triggered under simulated tumor microenvironmental conditions and should open new opportunities for potential multi stimuli-responsive drug delivery applications.

Therapeutic nanodendrites: current applications and prospects.

Multidisciplinary efforts in the field of nanomedicine for cancer therapy to provide solutions to common limitations of traditional drug administration such as poor bioaccumulation, hydrophobicity, and nonspecific biodistribution and targeting have registered very promising progress thus far. Currently, a new class of metal nanostructures possessing a unique dendritic-shaped morphology has been designed for improved therapeutic efficiency. Branched metal nanoparticles or metal nanodendrites are credited to present promising characteristics for biomedical applications owing to their unique physicochemical, optical, and electronic properties. Nanodendrites can enhance the loading efficiency of bioactive molecules due to their three-dimensional (3D) high surface area and can selectively deliver their cargo to tumor cells using their stimuli-responsive properties. With the ability to accumulate sufficiently within cells, nanodendrites can overcome the detection and clearance by glycoproteins. Moreover, active targeting ligands such as antibodies and proteins can as well be attached to these therapeutic nanodendrites to enhance specific tumor targeting, thereby presenting a multifunctional nanoplatform with tunable strategies. This mini-review focuses on recent developments in the understanding of metallic nanodendrite synthesis, formation mechanism, and their therapeutic capabilities for next-generation cancer therapy. Finally, the challenges and future opportunities of these fascinating materials to facilitate extensive research endeavors towards the design and application were discussed.

A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy.

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.