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.

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.

Synthetic routes to theranostic applications of carbon-based quantum dots.

Background and Purpose: Modern technologies are making advanced paths to address emerging issues. The development of carbon dots (CDs) technology at a tiny level has been researched to have made impeccable strides in advancing the modern scientific field, especially in nanomedicine. Experimental Approach: Researchers have gained much attention on CDs of their unique properties in the synthesis, easy surface modifications, excellent optical properties, low toxicity, and water solubility. Doping carbon dots with other elements makes them more convenient for their use in the medical sector. Key Results: The manuscript provides a detailed discussion of the two main methods, including the hydrothermal pathway. CDs are synthesized bottom-up by building up molecules at the atomic scale and top-down by transforming large carbon particles into nanoscale dimensions. Conclusion: The present article discussed the role, importance, and recent advancements in the synthesis of CDs, by using various approaches giving importance to the hydrothermal process. Recent investigations, their mechanism, and theranostic applications have also been reported.

Infections associated with SARS-CoV-2 exploited via nanoformulated photodynamic therapy.

Background and purpose: The pandemic of COVID-19 has highlighted the need for managing infectious diseases, which spreads by airborne transmission leading to serious health, social, and economic issues. SARS-CoV-2 is an enveloped virus with a 60-140 nm diameter and particle-like features, which majorly accounts for this disease. Expanding diagnostic capabilities, developing safe vaccinations with long-lasting immunity, and formulating effective medications are the strategies to be investigated. Experimental approach: For the literature search, electronic databases such as Scopus, Google Scholar, MEDLINE, Embase, PubMed, and Web of Science were used as the source. Search terms like 'Nano-mediated PDT,' 'PDT for SARS-CoV-2', and 'Nanotechnology in treatment for SARS-CoV-2' were used. Out of 275 initially selected articles, 198 were chosen after the abstract screening. During the full-text screening, 80 papers were excluded, and 18 were eliminated during data extraction. Preference was given to articles published from 2018 onwards, but a few older references were cited for their valuable information. Key results: Synthetic nanoparticles (NPs) have a close structural resemblance to viruses and interact greatly with their proteins due to their similarities in the configurations. NPs had previously been reported to be effective against a variety of viruses. In this way, with nanoparticles, photodynamic therapy (PDT) can be a viable alternative to antibiotics in fighting against microbial infections. The protocol of PDT includes the activation of photosensitizers using specific light to destroy microorganisms in the presence of oxygen, treating several respiratory diseases. Conclusion: The use of PDT in treating COVID-19 requires intensive investigations, which has been reviewed in this manuscript, including a computational approach to formulating effective photosensitizers.

Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum.

It is evident that site-specific systemic drug delivery can reduce side effects, systemic toxicity, and minimal dosage requirements predominantly by delivering drugs to particular pathological sites, cells, and even subcellular structures. The endoplasmic reticulum (ER) and associated cell organelles play a vital role in several essential cellular functions and activities, such as the synthesis of lipids, steroids, membrane-associated proteins along with intracellular transport, signaling of Ca2+, and specific response to stress. Therefore, the dysfunction of ER is correlated with numerous diseases where cancer, neurodegenerative disorders, diabetes mellitus, hepatic disorder, etc., are very common. To achieve satisfactory therapeutic results in certain diseases, it is essential to engineer delivery systems that can effectively enter the cells and target ER. Nanoparticles are highly biocompatible, contain a variety of cargos or payloads, and can be modified in a pliable manner to achieve therapeutic effectiveness at the subcellular level when delivered to specific organelles. Passive targeting drug delivery vehicles, or active targeting drug delivery systems, reduce the nonselective accumulation of drugs while reducing side effects by modifying them with small molecular compounds, antibodies, polypeptides, or isolated bio-membranes. The targeting of ER and closely associated organelles in cells using nanoparticles, however, is still unsymmetrically understood. Therefore, here we summarized the pathophysiological prospect of ER stress, involvement of ER and mitochondrial response, disease related to ER dysfunctions, essential therapeutics, and nanoenabled modulation of their delivery to optimize therapy.

Cancer therapy with iRGD as a tumor-penetrating peptide.

One of the primary threats in tumor treatment revolves around the limited ability to penetrate tumor sites, leading to reduced therapeutic effectiveness, which remains a critical concern. Recently gaining importance are novel peptides, namely CRGDK/RGPD/EC (iRGD), that possess enhanced tumor-penetrating and inhibitory properties. These peptides specifically target and penetrate tumors by binding to αvß integrins, namely αvß3 and αvß5, as well as NRP-1 receptors. Remarkably abundant on both the vasculature and tumor cell surfaces, these peptides show promising potential for improving tumor treatment outcomes. As a result, iRGD penetrated deep into the tumor tissues with biological products, contrast agents (imaging agents), antitumor drugs, and immune modulators after co-injecting them with peptides or chemically linked to peptides. The synthesis of iRGD peptides is a relatively straightforward process compared to the synthesis of other traditional peptides, and they significantly improved tumor tissue penetration inhibiting tumor metastasis effectively. Recent studies demonstrate the effectiveness of iRGD-driven dual-targeting chemotherapeutics on cancer cells, and the nanocarriers were modified with iRGD, serving as a favorable delivery strategy of payloads for deeper tumor regions. This review aims to provide an overview to emphasize the recent advancements and advantages of iRGD in treating and imaging various cancers.

Combinatorial Effect of Doxorubicin Entrapped in Alginate-Chitosan Hybrid Polymer and Cerium Oxide Nanocomposites on Skin Cancer Management in Mice.

Conventional chemotherapeutic drugs are used for cancer management, but recently nanoparticles have also been shown to contribute towards controlling cancer cell proliferation. In the present study, we focussed on analyzing the combinatorial effect of Cerium oxide (CeO2) nanoparticles and Doxorubicin (Dox) on melanoma cancer cells in vitro and in vivo. We entrapped CeO2, Dox, and CeO2+Dox in a hybrid polymer matrix of alginate and chitosan (Alg-Cs) and used them in both in vitro and in vivo studies to compare their anticancer effect. Scratch assay using A549 lung cancer cells showed delayed wound healing when exposed to a low and high dose of CeO2 +Dox, compared to individual components. In order to determine a safe dose of the nanoformulations, zebrafish embryos were used. Further, in vivo, testing was done on Swiss albino female mice where the melanoma was induced by applying Benzopyrene followed by UV irradiation. The animals were treated with CeO2, Dox, and CeO2+ Dox that were entrapped in Alg-Cs for further 21 days. From both in vivo and in vitro results, we concluded that CeO2 and Dox in combination had superior therapeutic efficiency in cancer cells and animals than the nude drugs.

Rhodamine-Conjugated Anti-Stokes Gold Nanoparticles with Higher ROS Quantum Yield as Theranostic Probe to Arrest Cancer and MDR Bacteria.

Photodynamic therapy (PDT) has recently become significant as a clinical modality for cancer therapy and multidrug-resistant (MDR) infections, replacing conventional chemotherapy and radiation therapy protocols. PDT involves the excitation of certain nontoxic molecules called photosensitizers (PS), applying a specific wavelength of light to generate reactive oxygen species (ROS) to treat cancer cells and other pathogens. Rhodamine 6G (R6G) is a well-known laser dye with poor aqueous solubility, and lower sensitivity poses an issue in using PS for PDT. Nanocarrier systems are needed to deliver R6G to cancer targets since PDT requires a higher accumulation of PS. It was found that R6G-conjugated gold nanoparticles (AuNP) have a higher ROS quantum yield of 0.92 compared to 0.3 in an aqueous R6G solution, increasing their potency as PS. Cytotoxicity assessment on A549 cells and antibacterial assay on MDR Pseudomonas aeruginosa collected from a sewage treatment plant are the evidence to support efficient PDT. In addition to their enhanced quantum yields, the decorated particles are effective in generating fluorescent signals that can be used for cellular imaging and real-time optical imaging, and the presence of AuNP is a valuable addition to CT imaging. Furthermore, the fabricated particle exhibits anti-Stokes properties, which makes it suitable for use as a background-free biological imaging agent. As a result, R6G-conjugated AuNP is an effective theranostic agent that prevents the progression of cancer and MDR bacteria, along with contrasting abilities in medical imaging with minimal toxicity observed in in vitro and in vivo assays using zebrafish embryos.

Alginate-Derivative Encapsulated Carbon Coated Manganese-Ferrite Nanodots for Multimodal Medical Imaging.

Carbon-decorated ferrite nanodots (MNF@Cs) have been enhanced with superparamagnetism and higher fluorescence quantum yield by encapsulation with an alginate derivative to create a cost-effective and less toxic multimodal contrast agent for replacing the conventional heavy metal Gd-containing contrast agent used in MR imaging. The novel surface-engineered particles (MNF@C-OSAs), devoid of labels, can simultaneously provide both longitudinal and transverse relaxation-based magnetic resonance imaging (MRI) and fluorescence emission. According to the findings of in vitro studies, the calculated molar relaxivities and the molar radiant efficiencies are indicative of the multimodal efficacy of MNF@C-OSA as compared with MNF@C particles and conventional contrast agents used in medical imaging. MNF@C-OSAs were shown to be significantly biocompatible and negligibly toxic when assessed against A549 cells and zebrafish embryos, indicating their potential for use as theranostic agents.

Nanoformulation of Tetrapyrroles Derivatives in Photodynamic Therapy: A Focus on Bacteriochlorin.

Photodynamic therapy (PDT) is a well-known remedial treatment for cancer, infections, and various other diseases. PDT uses nontoxic dyes called photosensitizers (PS) that are activated in visible light at the proper wavelength to generate ROS (reactive oxygen species) that aid in killing tumor cells and destroying pathogenic microbes. Deciding a suitable photosensitizer is essential for enhancing the effectiveness of photodynamic therapy. It is challenging to choose the photosensitizer that is appropriate for specific pathological circumstances, such as different cancer species. Porphyrin, chlorin, and bacteriochlorin are tetrapyrroles used with proper functionalization in PDT, among which some compound has been clinically approved. Most photosensitizers are hydrophobic, have minimum solubility, and exhibit cytotoxicity due to the dispersion in biological fluid. This paper reviewed some nanotechnology-based strategies to overcome these drawbacks. In PDT, metal nanoparticles are widely used due to their enhanced surface plasmon resonance. The self-assembled nano-drug carriers like polymeric micelles, liposomes, and metal-based nanoparticles play a significant role in solubilizing the photosensitizer to make them biocompatible.