nan Nafiujjaman

Surface Coating of Graphene Quantum Dots Using Mussel-Inspired Polydopamine for Biomedical Optical Imaging

Because of the superiority of GQDs (graphene quantum dots) in biomedical imaging, in terms of biocompatibility and toxicity of semiconductor quantum dots, GQDs bring new opportunities for the diagnosis and detection of diseases. In this study, we synthesized photoluminescent (PL) graphene quantum dots (GQDs) through a simple exfoliation and oxidation process, and then coated them with polydopamine (pDA) for enhanced stability in water and low toxicity in vivo. From the results, the GQDs coated with pDA showed an excellent stability of PL intensity. It showed that the PL intensity of noncoated GQDs in PBS solution rapidly decreased with time, resulting in a 45% reduction of the PL intensity for 14 days of incubation in PBS solution. After coating with polydopamine, PL intensities of polydopamine-coated GQDs was maintained more stably for 14 days compared with uncoated GQDs. We have observed the in vitro and in vivo biocompatibility of pDA-coated GQDs in nude mice. The overall observation revealed that pDA-coated GQDs could be used as a long-term optical imaging agent as well as a biocompatible drug carrier.

Bioapplication of graphene oxide derivatives: drug/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges

Due to the wide range and various applications of graphene in multidisciplinary fields, such as electronics, solar cells, biomedicine, bioengineering, drug delivery, gene delivery and semiconductors, graphene and its derivatives have attracted most significant interest of diverse group of scientists in the last decades. Besides numerous applications in electrical and mechanical fields, their non-invasive biomedical imaging properties allow their wide-spread biological applications. Optical imaging probes play a pivotal role in early cancer detection, image based surgery, disease diagnosis and cellular imaging. Graphene has been widely studied in drug delivery systems due to its unique features and comparatively less/non-toxic properties in biological systems, thus promoting graphene quantum dots as potential organic optical imaging agents to substitute toxic cadmium or tellurium quantum dots. Many groups have also focused on different polymeric modification strategies to enhance the biocompatibility as well as the applications of graphene. In this review, we have summarized recent advances in graphene-based applications, and focused on the relation between chemical structure and polymeric modification with bio-safety issues. The lack of adequate biosafety studies and understanding of the interaction between graphene derivatives and biomolecules has hindered their progress in biomedical and biological applications. To proceed with biological applications of graphene derivatives, such as the development of graphene-based therapeutics and drug delivery systems, the research community must understand how graphene derivatives interact with cell lines and how they accumulate into cells. We also need to learn the fate of graphene derivatives in vivo once it invasively enters into a biological system.

A photosensitizer-conjugated magnetic iron oxide/gold hybrid nanoparticle as an activatable platform for photodynamic cancer therapy

A multifunctional nanomedicine combining magnetic resonance imaging (MRI) and photodynamic therapy (PDT) functionalities is a promising integrated platform that allows for targeted drug delivery, noninvasive monitoring of therapeutic responses, and simultaneous cancer diagnosis and treatment. A hybrid nanoparticle (NP) system with a core/shell-structured magnetic iron oxide/gold (Fe3O4/Au) NP and a photosensitizer (PS)-conjugated heparin surface layer is investigated as a novel multifunctional carrier in PDT. A thiolated heparin-pheophorbide a (PhA) conjugate (H-PhA), which is a macromolecular PS, is synthesized and introduced onto the NP surface through a gold-thiol interaction. The photoactivity of the PhA moieties on the NP surface is significantly suppressed by the quenching effect of the Fe3O4/Au NP. However, their photoactivity can be restored in a glutathione (GSH)-rich intracellular environment, which allows GSH-mediated switchable photoactivity in the hybrid NP system. As a result, marked phototoxicity and strong fluorescence signals are observed in NP-treated A549 cells under light irradiation. In an animal tumor model, Fe3O4/Au/H-PhA NPs are efficacious in photodynamic cancer treatment and exhibit prolonged circulation characteristics, enhanced tumor specificity, and higher therapeutic efficacy compared with free PhA. In addition, in vitro MRI studies reveal that the NPs could potentially serve as MRI contrast agents in cancer diagnosis and may be used to monitor the photodynamic treatment response used to accurately guide light irradiation. The present findings show that the Fe3O4/Au/H-PhA NP is a promising nanomedicine platform in PDT and cancer diagnosis.

Ternary graphene quantum dot–polydopamine–Mn3O4 nanoparticles for optical imaging guided photodynamic therapy and T1-weighted magnetic resonance imaging

Imaging-guided therapy, which bridges treatment and diagnosis, plays an important role in overcoming the limitations of classical cancer therapy. To provide a more exact location of the tumor and to reduce side effects to normal tissues, a multifunctional probe was designed to serve as both an imaging agent and a therapeutic agent. Ternary hybrid nanoparticles comprised of visible red-responsive graphene, the T1-weighted magnetic resonance imaging (MRI) agent Mn3O4 and a mussel-inspired linker polydopamine. The conjugation of graphene to Mn3O4 through polydopamine enhanced the water solubility of Mn3O4, enabling an efficient uptake by cancer cells as well as tumor accumulation when the nanoparticles were intravenously administered into mice. These nanoparticles, when localized at a tumor site, exhibited low cytotoxicity in the dark, while light irradiation of the cancer cells transfected with the nanoparticles resulted in significant phototherapeutic effects, apparently by generating toxic reactive oxygen species. These nanoparticles also allowed excellent T1-weighted MR imaging in a human lung cancer xenograft model and were successfully used for combined visible red-imaging-guided photodynamic therapy and T1-weighted MRI.

Hybrid photoactive nanomaterial composed of gold nanoparticles, pheophorbide-A and hyaluronic acid as a targeted bimodal phototherapy

Modern cancer research is largely focused on the design and development of multifunctional nanomaterials for cancer therapy and diagnosis. In this study, we fabricated a theranostic nanomaterial known as a photomedicine that combines a photothermal therapy (PTT), gold nanoparticles (AuNPs), a photodynamic therapy (PDT), pheophorbide-A (PheoA), and a cancer-targeting agent, hyaluronic acid (HA); this photomedicine also acts as a bimodal phototherapy. The combination of AuNPs and PheoA exerts a synergistic effect on PTT and PDT when irradiated by a laser source with a specific excitation wavelength. When excited by an external laser source, the hybrid nanomedicine generates singlet oxygen from PheoA while simultaneously generating heat from the AuNP, thus demonstrating a higher efficacy than any of the individual agents. The presence of HA on the outer surface of the Au accelerates the cellular uptake of the nanomedicine through CD44 receptors and prevents nonspecific accumulation of the drug in non-cancerous cells. The multifunctional nanoparticles have a diameter of ∼70 nm and show constant stability in different conditions for up to a week of observation. In vitro and in vivo studies have demonstrated that multifunctional nanomaterials selectively target cells overexpressing CD44 receptor. In vitro photo-activity assays in the lung cancer cell line (A549) show that over 95% of the cells were dead upon laser irradiation. In brief, this newly developed nanomaterial rapidly accumulates in the tumor within 3 h of IV administration and inhibits tumor growth by 95% upon laser irradiation compared with a saline-treated tumor model observed for 24 days.

Design and strategies for bile acid mediated therapy and imaging

Bioinspired materials have received substantial attention across biomedical, biological, and drug delivery research because of their high biocompatibility and lower toxicity compared with synthetic materials. Bile acids, well-established biomimetic biomolecules, have been reported with respect to their potential applications as carriers of drugs or imaging contrast agents and, most importantly, as oral absorption enhancers. This review introduced the potential mechanisms involved in the oral absorption of bile acids and their derivatives and further focused on the intelligent applications of bile acids or modified bile acids that respond to biological cues as potential oral absorption enhancers for peptides and macromolecular drugs. Our investigations via the modifications of bile acids with various linkers have demonstrated their effects on the degree of oral absorption. Furthermore, we summarized the reports regarding the development of bile acid formulations for the oral delivery of optical imaging contrast agents for GI tract imaging, as well as anticancer drug delivery. Our opinions regarding the utilization of bile acids for biological and biomedical applications provide clear and concise guidance to investigators with respect to the merits and demerits of bile acid use and the selection of appropriate bile acids based on the requirements for improved biomedical applications.

Hemorheological characteristics of red blood cells exposed to surface functionalized graphene quantum dots.

Graphene quantum dots (GQDs) are potential candidates for various biomedical applications such as drug delivery, bioimaging, cell labeling, and biosensors. However, toxicological information on their effects on red blood cells (RBCs) and the mechanisms involved remain unexplored. To the best of our knowledge, our study is the first to investigate the toxicity effects of three GQDs with different surface functionalizations on the hemorheological characteristics of human RBCs, including hemolysis, deformability, aggregation, and morphological changes. RBCs were exposed to three different forms of GQDs (non-functionalized, hydroxylated, and carboxylated GQDs) at various concentrations (0, 500, 750, and 1000xa0μg/mL) and incubation times (0, 1, 2, 3, or 4xa0h). The rheological characteristics of the RBCs were measured using microfluidic-laser diffractometry and aggregometry. Overall, the hemolysis rate and rheological alterations of the RBCs were insignificant at a concentration less than 500xa0μg/mL. Carboxylated GQDs were observed to have more substantial hemolytic activity and caused abrupt changes in the deformability and aggregation of the RBCs than the non-functionalized or hydroxylated GQDs at concentrations >750xa0μg/mL. Our findings indicate that hemorheological assessments could be utilized to estimate the degree of toxicity to cells and to obtain useful information on safety sheets for nanomaterials.

Oral Gavage Delivery of PR8 Antigen with β-Glucan-Conjugated GRGDS Carrier to Enhance M-Cell Targeting Ability and Induce Immunity

Oral gavage is known as one of most convenient routes for therapeutic administration in comparison with other available routes such as intravenous, intra muscular, suppository, etc. An oral vaccine delivery system has additional potential as it may provide a convenient way to prevent infectious diseases by introducing optimum immunization in mucus. Although oral vaccine delivery has attracted tremendous interest in vaccine delivery research, various limitations have prevented its rate of progress up to the level that was initially expected. However, the major problems of oral vaccine delivery are vaccine instability and lack of absorbability, resulting from degradation of the sophisticated antigens in the acidic medium in the stomach. In order to obtain adequate microfold-cell (M-cell) targeting and uptake, the therapeutic material is required to pass through the stomach and reach the small intestine without degradation. In this project, we have introduced a conjugate of β-glucan and Glycine-Arginine-Glycine-Aspartic acid-Serine (GRGDS) that is effective for simultaneous protection of the antigen (PR8) and M-cell targeting. According to the experimental results, the cationic β-glucan-GRGDS conjugate can encapsulate a certain amount of anionic PR8 through electrostatic interaction, which forms nanoparticles with a range of diameter of 200-250 nm. Also, the PR8 incorporated nanoparticles showed high cell viability and stability in diverse environments. Finally, excellent M-cell targeting ability was verified in an in vitro M-cell model. Most importantly, the in vivo test obviously demonstrated the superiority of this system, which significantly increases antibody concentration in serum, intestine, and mucus as measured 21 days after immunization.

Synthesis of Nitrogen- and Chlorine-Doped Graphene Quantum Dots for Cancer Cell Imaging

In this study, we synthesized high quantum yield nitrogen and chlorine-doped graphene quantum dots (Cl-GQDs-N) for cancer cell imaging using simple and high production yield hydrothermal method from low-cost fructose. Prepared Cl-GQDs-N are about 30 nm in diameter and these Cl-GQDs-N display powerful blue color photoluminescence under the 365 nm UV lamp. We have further investigated their optical performances under various conditions. In vitro study shows no toxicity effect in normal and cancer cells treated with Cl-GQDs-N. Finally, we believe that our synthesized Cl-GQDs-N will bring more application opportunities in the field of bioimaging, optoelectronics and beyond.

Anticancer activity of Arkeshwara Rasa - A herbo-metallic preparation

Introduction: Though metal based drugs have been prescribed in Ayurveda for centuries to treat various diseases, such as rheumatoid arthritis and cancer, toxicity of these drugs containing heavy metal is a great drawback for practical application. So, proper scientific validation of herbo-metallic drugs like Arkeshwara Rasa(AR) have become one of the focused research arena of new drugs against cancers. Aim: To investigate the in vitro anticancer effects of AR. Materials and Methods: Anticancer activity of AR was investigated on two human cancer cell lines, which represent two different tissues (pancreas and skin). Lactate dehydrogenase (LDH) assay for enzyme activity and trypan blue assay for cell morphology were performed for further confirmation. Results: AR showed potent activity against pancreatic cancer cells (MIA-PaCa-2). LDH activity confirmed that AR was active against pancreatic cancer cells. Finally, it was observed that AR exhibited significant effects on cancer cells due to synergistic effects of different compounds of AR. Conclusion: The study strongly suggests that AR has the potential to be an anticancer drug against pancreatic cancer.