Harmony in nature's elixir: a comprehensive exploration of ethanol and nano-formulated extracts from Passiflora incarnata leaves: unveiling in vitro cytotoxicity, acute and sub-acute toxicity profiles in Swiss albino mice.

We analyzed the toxic effect of the ethanolic extract of Passiflora incarnata (EEP) and its nanoformulation (N-EEP) in the in vitro and in vivo models (zebrafish embryos and Swiss albino mice). The EEP composition was verified by phytochemical and GC-MS analysis. The synthesized N-EEP was characterized using UV-visible spectroscopy and scanning electron microscopy. In vitro results showed both EEP and N-EEP have a dose-dependent effect in L132 cells (normal embryonic lung cells). In zebrafish embryos, no developmental changes were observed for both EEP and N-EEP at 200 µg/ml. The acute and sub-acute toxicity of EEP and N-EEP was identified by oral administration in Swiss albino mice. A single-day oral dose of EEP and N-EEP at different concentrations was administered for acute toxicity, and changes in body weight, food, water intake, temperature, respiration rate, skin color changes, and eye color till 72 h was observed. In a sub-acute toxicity study, 28 days oral administration of different concentrations of EEP and N-EEP was done. Hematological analysis, serum hepatic biochemical parameter analysis, and histopathological analysis for the liver, kidney, spleen, intestine, and heart were performed. The results indicated that lower than 600 mg/kg of EEP and N-EEP can safely be used for the remediation of a spectrum of diseases.

Rhodamine 6G in Oxidized Sodium Alginate Polymeric Hydrogel for Photodynamically Inactivating Cancer Cells.

INTRODUCTION: As cancer therapy progresses, challenges remain due to the inherent drawbacks of conventional treatments such as chemotherapy, gene therapy, radiation therapy, and surgical removal. Moreover, due to their associated side effects, conventional treatments affect both cancerous and normal cells, making photodynamic therapy (PDT) an attractive alternative. METHODS: As a result of its minimal toxicity, exceptional specificity, and non-invasive characteristics, PDT represents an innovative and highly promising cancer treatment strategy using photosensitizers (PSs) and precise wavelength excitation light to introduce reactive oxygen species (ROS) in the vicinity of cancer cells. RESULTS: Poor aqueous solubility and decreased sensitivity of Rhodamine 6G (R6G) prevent its use as a photosensitizer in PDT, necessitating the development of oxidized sodium alginate (OSA) hydrogelated nanocarriers to enhance its bioavailability, targeted distribution, and ROS-quantum yield. The ROS quantum yield increased from 0.30 in an aqueous environment to 0.51 when using alginate-based formulations, and it was further enhanced to 0.81 in the case of OSA. CONCLUSION: Furthermore, the nanoformulations produced fluorescent signals suitable for use as cellular imaging agents, demonstrating contrast-enhancing capabilities in medical imaging and showing minimal toxicity.

Theranostic dye entrapped in an optimized blended-polymer matrix for effective photodynamic inactivation of diseased cells.

Despite the wide range of treatment options available for cancer therapy, including chemotherapy, radiation therapy, and surgical procedures, each of these treatments has a different side-effect profile and leaves the patient with no option but to choose. Due to their insensitivity and nonspecificity, conventional treatments damage normal cells together with cancer cells. In recent years, a significant amount of attention has been focused on photodynamic therapy (PDT) as a treatment for cancer and drug-resistant microbes. An activated photosensitizer is used as a part of the procedure along with oxygen molecules and a specific wavelength of light belonging to the visible or NIR spectral zone. A light-sensitive laser dye, rhodamine 6G (R6G), was used in the present study as a photosensitizer, taking a challenge to improve the aqueous solubility and ROS quantum yield using optimum concentration (160 mg/ml) of chitosan-alginate (Cs-Alg) blended polymeric nanoformulations. As evidenced by steady-state spectrophotometric and fluorometric measurements, ROS quantum yield increases three-fold over aqueous solution along with solubility gaining that was validated by PDT experiment using human epithelial carcinoma (KB) cell line. Phantom optical imaging was taken using the IVIS imaging system to establish the formulations as a fluorescence-based optical contrast agent, and zebrafish embryos were used to establish their safe in vivo use. The release profile of R6G was fitted using kinetic models, which followed the Non-Fickian kinetic profile. In conclusion, we recommend the formulations as a potential theranostic agent that will aid in PDT-based therapy in conjunction with optical imaging-based diagnosis.

Management of hypertension addressing hyperuricaemia: introduction of nano-based approaches.

Uric acid (UA) levels in blood serum have been associated with hypertension, indicating a potential causal relationship between high serum UA levels and the progression of hypertension. Therefore, the reduction of serum UA level is considered a potential strategy for lowering and mitigating blood pressure. If an individual is at risk of developing or already manifesting elevated blood pressure, this intervention could be an integral part of a comprehensive treatment plan. By addressing hyperuricaemia, practitioners may subsidize the optimization of blood pressure regulation, which illustrates the importance of addressing UA levels as a valuable strategy within the broader context of hypertension management. In this analysis, we outlined the operational principles of effective xanthine oxidase inhibitors for the treatment of hyperuricaemia and hypertension, along with an exploration of the contribution of nanotechnology to this field.

Unveiling the Role of Nano-Formulated Red Algae Extract in Cancer Management.

Cancer is one of the major causes of death, and its negative impact continues to rise globally. Chemotherapy, which is the most common therapy, has several limitations due to its tremendous side effects. Therefore, developing an alternate therapeutic agent with high biocompatibility is indeed needed. The anti-oxidative effects and bioactivities of several different crude extracts of marine algae have been evaluated both in vitro and in vivo. In the present study, we synthesized the aqueous extract (HA) from the marine algae Amphiroa anceps, and then, a liposome was formulated for that extract (NHA). The extracts were characterized using different photophysical tools like dynamic light scattering, UV-visible spectroscopy, FTIR, scanning electron microscopy, and GC-MS analysis. The SEM image revealed a size range of 112-185 nm for NHA and the GC-MS results showed the presence of octadecanoic acid and n-Hexadecanoic acid in the majority. The anticancer activity was studied using A549 cells, and the NHA inhibited the cancer cells dose-dependently, with the highest killing of 92% at 100 µg/mL. The in vivo studies in the zebrafish model showed that neither the HA nor NHA of Amphiroa anceps showed any teratogenic effect. The outcome of our study showed that NHA can be a potential drug candidate for inhibiting cancer with good biocompatibility up to a dose of 100 µg/mL.

Beneficial effects of bioinspired silver nanoparticles on zebrafish embryos including a gene expression study.

Background and purpose: Many sectors use nanoparticles and dispose of them in the aquatic environment without deciding the fate of these particles. Experimental approach: To identify a benign species of nanoparticles which can cause minimum harm to the aquatic environment, a comparative study was done with chemically synthesized silver nanoparticles (AgNPs) and green tea mediated synthesis (GT/AgNP) in both in vitro using human alveolar cancer cell line (A549) and normal cell line (L132), and in in vivo with zebrafish embryos. Key results: The in vitro studies revealed that GT/AgNPs were less toxic to normal cells than cancer cells. The GT/AgNPs showed high biocompatibility for zebrafish embryos monitored microscopically for their developmental stages and by cumulative hatchability studies. The reduced hatchability found in the AgNPs-treated group was correlated by differential gene expression of zebrafish hatching enzymes (ZHE) (ZHE1 and ZHE2). Conclusion: The results indicated that nanoparticles can affect the hatching of zebrafish embryos and elicit toxicity at the gene level.

Niosomal Bupropion: Exploring Therapeutic Frontiers through Behavioral Profiling.

Bupropion (Bup) belongs to the norepinephrine-dopamine reuptake inhibitor (NDRI) class and it is the only FDA-approved drug of its class for the treatment of major depressive disorder (MDD), sold under the name of Wellbutrin. Although bupropion is effective in suppressing the symptoms, its regular use and overdose might lead to seizures and liver failure. Thus, we aimed to nanoformulate bupropion onto a niosomal vesicle to improve its efficacy and achieve the same therapeutic effect at lower scheduled doses. A thin film hydration method was adopted to synthesize and optimize Bup entrapped niosomes using three different surfactants of the sorbitan ester series (Span 20, 40, and 60) in combination with cholesterol. The optimization data determined that the niosome formulated with a cholesterol-to-surfactant ratio of 1:1.5 is the most stable system, with the Bup entrapped niosomes containing Span 20 (Bup@N20C) exhibiting minimal in vitro and in vivo toxicity, and demonstrating the sustained release of Bup in artificial cerebrospinal fluid (ACSF). The Bup@N20C formulation showed increased exploration activity and reduced irregular movements in reserpine-induced depression in the adult zebrafish model, suggesting the potential for mood improvement through the suppression of depression-like behavior which was established by statistical analysis and trajectory data. The Bup@N20C-treated group even surpasses the treatment effect of the positive control group and is comparable to the control group. Hence, it can be inferred that niosomal formulations of Bup represent a promising delivery system capable of achieving the brain delivery of the cargo by bypassing the blood-brain barrier facilitated by their small architectural structure.

Association of TIMP2 418 G/C and MMP Gene Polymorphism with Risk of Urinary Cancers: Systematic Review and Meta-analysis.

Aim: The matrix metalloproteinases (MMPs) inhibit tissue inhibitors of metalloproteinases (TIMPs), playing a notable role in various biological processes, and mutations in TIMP2 genes impact a variety of urinary cancers. In this study, we analyze and evaluate the potential involvement of the TIMP2 418 G/C and MMP gene polymorphism in the etiology of urinary cancer. Methodology: For suitable case-control studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. Incorporated into the analysis were case-control or cohort studies that documented the correlation between TIMP2 418 G/C and urological cancers. MetaGenyo served as the tool for conducting the meta-analysis, employing a fixed-effects model. The collective odds ratios, along with their corresponding 95% confidence intervals, were calculated and presented to assess the robustness of the observed associations. Results: A total of seven studies involving controls and cases out of recorded 1265 controls and 1154 cases were analyzed to ascertain the significant association of the TIMP2 gene with urologic cancer. No statistically significant correlation was observed between allelic, recessive, dominant, and overdominant models for the genetic variant under investigation. A 95% confidence interval (CI) and odds ratio (OR) were computed for each model, considering p-values <0.05. The OR and 95% CI for the allelic model were 0.99 and 0.77-1.27, respectively, whereas the respective values were 1.00 and 0.76-1.32 for the recessive model. In the dominant contrast model, OR and 95% CI were 1.09 and 0.62-1.90, while the same were 0.93 and 0.77-1.12 for the overdominant model. A funnel plot was used to reanalyze and detect the results as statically satisfactory. Conclusions: As a result of the data obtained, the TIMP2 gene polymorphism does not correlate statistically with cancer risk. The significance of this finding can only be confirmed using a large population, extensive epidemiological research, a comprehensive survey, and a better understanding of the molecular pathways associated.

Carbon Dots for Multiuse Platform: Intracellular pH Sensing and Complementary Intensified T1-T2 Dual Imaging Contrast Nanoprobes.

Measurement of pH in living cells is a great and decisive factor for providing an early and accurate diagnosis factor. Along with this, the multimodal transverse and longitudinal relaxivity enhancement potentiality over single modality within a single platform in the magnetic resonance imaging (MRI) field is a very challenging issue for diagnostic purposes in the biomedical field of application. Therefore, this work aims to design a versatile platform by fabricating a novel nanoprobe through holmium- and manganese-ion doping in carbon quantum dots (Ho-Mn-CQDs), which can show nearly neutral intracellular pH sensing and MRI imaging at the same time. These manufactured Ho-Mn-CQDs acted as excellent pH sensors in the near-neutral range (4.01-8.01) with the linearity between 6.01 and 8.01, which could be useful for the intracellular pH-sensing capability. An innumerable number of carboxyl and amino groups are present on the surface of the prepared nanoprobe, making it an excellent candidate for pH sensing through fluorescence intensity quenching phenomena. Cellular uptake and cell viability experiments were also executed to affirm the intracellular accepting ability of Ho-Mn-CQDs. Furthermore, with this pH-sensing quality, these Ho-Mn-CQDs are also capable of acting as T1-T2 dual modal imaging contrast agents in comparison with pristine Ho-doped and Mn-doped CQDs. The Ho-Mn-CQDs showed an increment of r1 and r2 relaxivity values simultaneously compared with only the negative contrast agent, holmium in holmium-doped CQDs, and the positive contrast agent, manganese in manganese-doped CQDs. The above-mentioned observations elucidate that its tiny size, excitation dependence of fluorescence behavior, low cytotoxicity, and dual modal contrast imaging capability make it an ideal candidate for pH monitoring in the near-neutral range and also as a dual modal MRI imaging contrast enhancement nanoprobe at the same time.

Preparation of titanium dioxide nanoparticles from Solanum Tuberosum peel extract and its applications.

The present study describes a method for the preparation of green titanium dioxide (TiO2) nanoparticles from the peel of Solanum tuberosum, commonly known as potato, and the potato peel being a kitchen waste. The green synthesized TiO2 (G- TiO2) nanoparticles were characterized using UV-visible spectroscopy, dynamic light scattering, scanning electron microscopy, TEM, XRD, and FTIR spectroscopy. The photocatalytic activity of the G- TiO2 nanoparticles was also shown using the dye bromophenol blue. To explore the biocompatibility of the G- TiO2, the cell viability in normal as well as cancer cells was assessed. Further, the in vivo toxicity of the G- TiO2 nanoparticles was assessed using zebrafish embryos. The novelty of the present invention is to utilize kitchen waste for a useful purpose for the synthesis of titanium dioxide nanoparticles which is known to have UV light scavenging properties. Moreover, the potato peel is a natural antioxidant and possesses a skin-lightening effect. A combination of the potato peel extract and titanium dioxide prepared using the extract will have a combinatorial effect for protecting UV light exposure to the skin and lightening the skin colour.

Advantages of nanomedicine over the conventional treatment in Acute myeloid leukemia.

Leukemia is a cancer of blood cells that mainly affects the white blood cells. In acute myeloid leukemia (AML) sudden growth of cancerous cells occurs in blood and bone marrow, and it disrupts normal blood cell production. Most patients are asymptomatic, but it spreads rapidly and can become fatal if left untreated. AML is the prevalent form of leukemia in children. Risk factors of AML include chemical exposure, radiation, genetics, etc. Conventional diagnostic methods of AML are complete blood count tests and bone marrow aspiration, while conventional treatment methods involve chemotherapy, radiation therapy, and bone marrow transplant. There is a risk of cancer cells spreading progressively to the other organs if left untreated, and hence, early diagnosis is required. The conventional diagnostic methods are time- consuming and have drawbacks like harmful side effects and recurrence of the disease. To overcome these difficulties, nanoparticles are employed in treating and diagnosing AML. These nanoparticles can be surface- modified and can be used against cancer cells. Due to their enhanced permeability effect and high surface-to-volume ratio they will be able to reach the tumour site which cannot be reached by traditional drugs. This review article talks about how nanotechnology is more advantageous over the traditional methods in the treatment and diagnosis of AML.

Phosphorus-carrying cascade molecules: inner architecture to biomedical applications.

Cascade molecules are nearly uniform-sized macromolecules of small molecules or linear polymer cores built around symmetric branching units. A wide range of biological properties can be achieved with phosphorus-containing dendrimers, depending on their terminal functions, ranging from biomaterials to imaging, drug delivery, and acting as a drug by themselves. This feature article presents significant examples of phosphorus-containing dendrimers used to develop biochips, support cell cultures, carry or deliver biomacromolecules and drugs, bioimaging, and combinational benefits. Because of the thermal stability, ferrocene function, and physical and chemical properties of phosphorus, dendrimers show greater rigidity, mobility, and strength. These dendrimers will be discussed as having a favorable effect on cell growths, especially on neuronal cells, as well as human immune cells like natural killer cells and monocytes, which have a crucial part in preventing cancerous and viral infections. Several phosphorus dendrimers are effective as drugs by themselves (drug per se) and show their activity against neurodegenerative diseases, cancer, inflammation, ocular hypertension, and transmissible spongiform encephalopathies (TSEs) in both in vivo and in vitro. The present review discusses the synthetic route, fabrications, and biomedical applications of phosphorus-containing dendrimers. The toxicity of these dendrimers was also reported.