Oral delivery of RNAi for cancer therapy.

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.

Bile acid linked ß-glucan nanoparticles for liver specific oral delivery of biologics.

Oral delivery remains one of the most convenient routes for drug administration compared to intravenous, intramuscular, and via suppositories. However, due to the risk of degradation, and proteolysis of molecules in the acidic gastric medium, as well as the difficulty of transporting large molecules through the intestinal membrane, more than half of the therapeutic molecules are prohibited for oral administration. Moreover, most of the large molecules and biological therapeutics are not available in oral dosage form due to their instability in the stomach and inability of intestinal absorption. To achieve expected bioavailability, an orally administered therapeutic molecule must be protected within the stomach, and transportation facilitated via the small intestine. In this project, we have introduced a hybrid carrier, composed of Taurocholic Acid (TA) and ß-Glucan (TAG), that is shown to be effective for the simultaneous protection of the biologics in acidic buffer and simulated gastric juice as well as facilitate enhanced absorption and transportation via the small intestine. In this project, we have used an eGFP encoded plasmid as a model biologic to prepare particles mediated with TAG. TAG show the potential of enhancing transfection and expression of eGFP as we have observed two fold higher expression in the cell upon coincubation for 4 h. In vivo studies on orally dosed mice showed that eGFP expression in the liver was significantly higher in TAG containing particles compared to particles without TAG. The findings suggest that the TAG carrier is capable of not only preserving biologics but also transporting them more efficiently to the liver. As a result, this strategy can be employed for a variety of liver-targeted therapeutic delivery to treat a variety of liver diseases.

Potential Antiviral Properties of Industrially Important Marine Algal Polysaccharides and Their Significance in Fighting a Future Viral Pandemic.

Over the decades, the world has witnessed diverse virus associated pandemics. The significant inhibitory effects of marine sulfated polysaccharides against SARS-CoV-2 shows its therapeutic potential in future biomedical applications and drug development. Algal polysaccharides exhibited significant role in antimicrobial, antitumor, antioxidative, antiviral, anticoagulant, antihepatotoxic and immunomodulating activities. Owing to their health benefits, the sulfated polysaccharides from marine algae are a great deal of interest globally. Algal polysaccharides such as agar, alginate, carrageenans, porphyran, fucoidan, laminaran and ulvans are investigated for their nutraceutical potential at different stages of infection processes, structural diversity, complexity and mechanism of action. In this review, we focus on the recent antiviral studies of the marine algae-based polysaccharides and their potential towards antiviral medicines.

Highly Sensitive Electrochemical Biosensor Using Folic Acid-Modified Reduced Graphene Oxide for the Detection of Cancer Biomarker.

The detection of cancer biomarkers in the early stages could prevent cancer-related deaths significantly. Nanomaterials combined with biomolecules are extensively used in drug delivery, imaging, and sensing applications by targeting the overexpressed cancer proteins such as folate receptors (FRs) to control the disease by providing earlier treatments. In this investigation, biocompatible reduced graphene oxide (rGO) nanosheets combined with folic acid (FA)-a vitamin with high bioaffinity to FRs-is utilized to develop an electrochemical sensor for cancer detection. To mimic the cancer cell environment, FR-ß protein is used to evaluate the response of the rGO-FA sensor. The formation of the rGO-FA nanocomposite was confirmed through various characterization techniques. A glassy carbon (GC) electrode was then modified with the obtained rGO-FA and analyzed via differential pulse voltammetry (DPV) for its specific detection towards FRs. Using the DPV technique, the rGO-FA-modified electrode exhibited a limit of detection (LOD) of 1.69 pM, determined in a linear concentration range from 6 to 100 pM. This excellent electrochemical performance towards FRs detection could provide a significant contribution towards future cancer diagnosis. Moreover, the rGO-FA sensing platform also showed excellent specificity and reliability when tested against similar interfering biomolecules. This rGO-FA sensor offers a great promise to the future medical industry through its highly sensitive detection towards FRs in a fast, reliable, and economical way.

Graphene-based 3D scaffolds in tissue engineering: fabrication, applications, and future scope in liver tissue engineering.

Tissue engineering embraces the potential of recreating and replacing defective body parts by advancements in the medical field. Being a biocompatible nanomaterial with outstanding physical, chemical, optical, and biological properties, graphene-based materials were successfully employed in creating the perfect scaffold for a range of organs, starting from the skin through to the brain. Investigations on 2D and 3D tissue culture scaffolds incorporated with graphene or its derivatives have revealed the capability of this carbon material in mimicking in vivo environment. The porous morphology, great surface area, selective permeability of gases, excellent mechanical strength, good thermal and electrical conductivity, good optical properties, and biodegradability enable graphene materials to be the best component for scaffold engineering. Along with the apt microenvironment, this material was found to be efficient in differentiating stem cells into specific cell types. Furthermore, the scope of graphene nanomaterials in liver tissue engineering as a promising biomaterial is also discussed. This review critically looks into the unlimited potential of graphene-based nanomaterials in future tissue engineering and regenerative therapy.

Acoustic cavitation induced generation of stabilizer-free, extremely stable reduced graphene oxide nanodispersion for efficient delivery of paclitaxel in cancer cells.

Graphene is one of the highly explored nanomaterials due to its unique and extraordinary properties. In this study, by utilizing a hydrothermal reduction method, graphene oxide (GO) was successfully converted to reduced graphene oxide (RGO) without using any toxic reducing agents. Following this, with the use of ultrasonic cavitation, profoundly stable few layer thick RGO nanodispersion was generated without employing any stabilizers or surfactants. During ultrasonication, shockwaves from the collapse of bubbles cause a higher dispersing energy to the graphene nanosheets which surpass the forces of Van der Waal's and π-π stacking and thus pave the way to form a stable aqueous nanodispersion of graphene. Ultrasonication systems with different power intensity have been employed to determine the optimum conditions for obtaining the most stable RGO dispersion. The optimised conditions of ultrasonic treatments led to the development of a very stable reduced graphene oxide (RGO) aqueous dispersion. The stability was observed for two years and was analyzed by using Zetasizer by measuring the particle size and zeta potential at regular intervals and found to have exceptional stability. The excellent stability at physiological pH promotes its utilization in nano drug delivery application as a carrier for Paclitaxel (Ptx), an anticancer drug. The in vitro cytotoxicity analysis of Ptx loaded RGO nanodispersion by MTT assay performed on the cell lines revealed the potential of the nanodispersion as a suitable drug carrier. Studies on normal lung cells, MRC-5 and nasopharyngeal cancer cells, HK-1 supported the biocompatibility of RGO-Ptx towards normal cell line. This investigation shows the potential of exceptionally stable RGO-Ptx nanodispersion in nano drug delivery applications.

Sonochemical and sustainable synthesis of graphene-gold (G-Au) nanocomposites for enzymeless and selective electrochemical detection of nitric oxide.

In this study, a sonochemical approach was utilised for the development of graphene-gold (G-Au) nanocomposite. Through the sonochemical method, simultaneous exfoliation of graphite and the reduction of gold chloride occurs to produce highly crystalline G-Au nanocomposite. The in situ growth of gold nanoparticles (AuNPs) took place on the surface of exfoliated few-layer graphene sheets. The G-Au nanocomposite was characterised by UV-vis, XRD, FTIR, TEM, XPS and Raman spectroscopy techniques. This G-Au nanocomposite was used to modify glassy carbon electrode (GCE) to fabricate an electrochemical sensor for the selective detection of nitric oxide (NO), a critical cancer biomarker. G-Au modified GCE exhibited an enhanced electrocatalytic response towards the oxidation of NO as compared to other control electrodes. The electrochemical detection of NO was investigated by linear sweep voltammetry analysis, utilising the G-Au modified GCE in a linear range of 10-5000µM which exhibited a limit of detection of 0.04µM (S/N=3). Furthermore, this enzyme-free G-Au/GCE exhibited an excellent selectivity towards NO in the presence of interferences. The synergistic effect of graphene and AuNPs, which facilitated exceptional electron-transfer processes between the electrolyte and the GCE thereby improving the sensing performance of the fabricated G-Au modified electrode with stable and reproducible responses. This G-Au nanocomposite introduces a new electrode material in the sensitive and selective detection of NO, a prominent biomarker of cancer.