In situ thermosensitive H2O2/NO self-sufficient hydrogel for photothermal ferroptosis of triple-negative breast cancer.

L-Arginine (LA), a semi-essential amino acid in the human body, holds significant potential in cancer therapy due to its ability to generate nitric oxide (NO) continuously in the presence of inducible NO synthase (iNOS) or reactive oxygen species (ROS). However, the efficiency of NO production in tumor tissue is severely constrained by the hypoxic and H2O2-deficient tumor microenvironment (TME). To address this issue, we have developed calcium peroxide (CaO2) nanoparticles capable of supplying O2/H2O2, which encapsulate and oxidize an LA-modified lipid bilayer to enable controlled localized NO generation in the presence of ROS, synergising with a ferroptosis inducer, RSL-3 (CPIR NPs). The synthesized nanoparticles were tested in vitro for their anticancer activity in 4T1 cells. To address challenges related to specificity and frequent dosing, we developed an in situ thermosensitive injectable hydrogel incorporating CPIR nanoparticles. Cross-linking at 60 °C creates a self-sufficient formulation, releasing NO/H2O2 to combat tumor hypoxia. RSL-3 induces ferroptosis, contributing to a synergistic photothermal effect and eliminating tumor in vivo.

Barium Sulfate Nanocomposites for Bioimaging and Chemo-photothermal Therapy of Physiologically Aggravated Lung Adenocarcinoma Cells.

Cancer is a complex disease that displays physiomorphological transformation in different surrounding microenvironments. Therefore, the single treatment modalities are relatively less effective, and their efficiency varies with tumor cell physiology, leading to the development of tumor resistance. Combinatorial therapeutic approaches, such as chemo-photothermal therapy, are promising for efficiently mitigating tumor progression irrespective of cancer physiology. Nanotechnology has played a significant role in this regard. Therefore, the present study reports the synthesis of poly(acrylic acid)-tetraethylene glycol (PAA-TEG)-coated BaSO4 nanoparticles (NPs) with enhanced solubility, dispersibility, and X-ray attenuation. Next, nanocomposites (NCs) are synthesized by loading BaSO4 NPs with the therapeutic drug triiodobenzoic acid (Tiba) and the photosensitizer IR780 using a lipid coating. These fabricated NCs are analyzed for dual-modal imaging (fluorescence and X-ray-based imaging) properties and chemo-phototherapeutic ability against two-dimensional (2D) and three-dimensional (3D) cultures of A549 cells. Furthermore, A549 cells are morphologically and physiologically aggravated into potent malignant cells using tobacco leaf extract (TE), and the variation in the therapeutic effect of NCs compared to cisplatin is determined. The synthesized NCs display enhanced encapsulation and excellent synergistic anticancer activity through the generation of reactive oxygen species (ROS), mitochondrial damage, and genotoxicity. Also, the NCs are more potent in inhibiting cancer cell growth than cisplatin, and their impact is unaltered in the presence or absence of TE pretreatment of A549 cells. The present study holds significant potential for various theranostic applications, which are highly desired for laparoscopic image-guided lung cancer therapy.

A comprehensive review of 3D cancer models for drug screening and translational research.

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research. In addition to cancer cells, a range of other factors include the stroma, density and composition of extracellular matrix, cancer-associated immune cells (e.g., cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions, and a number of other factors (e.g., tumor vasculature and tumor-like microenvironment in vivo) has been widely ignored in the 2D concept of culture. Despite this knowledge, the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials. This review discusses the immense importance of tumor microenvironment (TME) recapitulation in cancer research, prioritizing the individual roles of TME elements in cancer histopathology. The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement, components, and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials, some of which are discussed here. Furthermore, it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors. Furthermore, this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.

Tailoring Phage Nanosomes for Enhanced Theranostic Properties of Near Infrared Dyes.

Near-infrared (NIR) phototherapies offer noninvasive, cost-effective solutions for treating tumors and microbial infections. However, organic NIR dyes commonly used suffer from solubility and stability issues requiring frequent dosing. We address this challenge by exploring the bacteriophage-mediated enhancement of NIR dye properties. Upon encapsulation within phage nanosomes, IR780 and Indocyanine green (ICG), with similar optical properties but distinct water solubility and exhibit enhanced UV-vis absorbance and photothermal transduction efficacy compared to liposomes. Experimental characterization corroborated with all-atom molecular dynamics simulations imprints the nanoscale structure, solubility, dynamics, and binding of these NIR dye molecules to the membrane and protein molecules present in Phage capsid. These NIR dye-loaded phage nanosomes, coencapsulated with mitoxantrone, demonstrate enhanced anticancer activity, and when combined with amphotericin B, these dye molecules exhibit superior photothermal effects against fungal infections. Our findings present a simple and efficient approach for tuning the photothermal performance of existing NIR dyes through a rational design for enhanced therapeutic outcomes.

Sodium copper chlorophyllin-loaded chitosan nanoparticle-based photodynamic therapy for B16 melanoma cancer cells.

Melanoma is one of the most aggressive and fatal skin cancers owing to its ability to metastasize and develop resistance to chemotherapy. Photodynamic therapy (PDT) is a minimally noninvasive treatment modality comprising photosensitizers (PSs), light sources, and endogenous molecular oxygen that exert a localized cytotoxic effect on cancer cells. The current study explores the therapeutic potential of sodium copper chlorophyllin-loaded chitosan nanoparticles (CH-SCC NPs) along with handheld laser-based PDT on B16 cancer cells. A modified chlorophyll derivative identified as sodium copper chlorophyllin (SCC) is a dietary supplement that has anticancer properties. Herein, we have synthesized CH-SCC NPs using the ionic gelation method to enhance the PS's bioavailability and efficiency. Chitosan nanoparticles exhibited high biocompatibility in a normal cell line L929, zebrafish, and chick embryos, and were successfully employed to deliver the SCC to cancer cells. CH-SCC NPs showed an enhanced PDT effect that killed approximately 80%-85% of B16 cells. CH-SCC NPs in combination with a handheld portable laser source showed significant therapeutic potential against the B16 skin cancer cell line. The experimental findings further strengthen our device-repurposing strategy, which suggests that SCC nanoformulations along with handheld laser can be a suitable treatment for skin cancer even in remote areas where power source and treatment cost can be a limitation.

Omeprazole-Loaded Copper Nanoparticles for Mitochondrial Damage Mediated Synergistic Anticancer Activity against Melanoma Cells.

Metallic nanoparticles are promising candidates for anticancer therapies. Among the different metallic systems studied, copper is an affordable and biologically available metal with a high redox potential. Copper-based nanoparticles are widely used in anticancer studies owing to their ability to react with intracellular glutathione (GSH) to induce a Fenton-like reaction. However, considering the high metastatic potential and versatility of the tumor microenvironment, modalities with a single therapeutic agent may not be effective. Hence, to enhance the efficiency of chemotherapeutic drugs, repurposing them or conjugating them with other modalities is essential. Omeprazole is an FDA-approved proton pump inhibitor used in clinics for the treatment of ulcers. Omeprazole has also been studied for its ability to sensitize cancer cells to chemotherapy and induce apoptosis. Herein, we report a nanosystem comprising of copper nanoparticles encapsulating omeprazole (CuOzL) against B16 melanoma cells. The developed nanoformulation exerted significant synergistic anticancer activity when compared with either copper nanoparticles or omeprazole alone by inducing cell death through excessive ROS generation and subsequent mitochondrial damage.

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

Tuning the Flavin Core via Donor Appendage for Selective Subcellular Bioimaging and PDT Application.

Herein, we report a novel flavin analogue as singular chemical component for lysosome bioimaging, and inherited photosensitizer capability of the flavin core was demonstrated as a promising candidate for photodynamic therapy (PDT) application. Fine-tuning the flavin core with the incorporation of methoxy naphthyl appendage provides an appropriate chemical design, thereby offering photostability, selectivity, and lysosomal colocalization, along with the aggregation-induced emissive nature, making it suitable for lysosomal bioimaging applications. Additionally, photosensitization capability of the flavin core with photostable nature of the synthesized analogue has shown remarkable capacity for generating reactive oxygen species (ROS) within cells, making it a promising candidate for photodynamic therapy (PDT) application.

Self-assembled IR dye/mitoxantrone loaded Porphysomes nanosystem for enhanced combinatorial chemo-photothermal cancer therapy.

Chemo-photothermal therapy (PTT) is an emerging non-invasive cancer treatment modality. Light-responsive porphysomes (DPP IR Mtx @Lipo NPs) nanosystems ablate breast cancer cells upon oxidative stress and hyperthermia. The unique self-assembled porphysomes were formed spherical shape in the size range of 150 ± 30 nm formed by the co-assembly of porphyrins along with IR 775 and chemotherapeutic drug, Mitoxantrone (Mtx), forming a camouflaged nanosystem (DPP IR Mtx @Lipo NPs, porphysomes). The advent of the prepared porphysomes aids in proper tuning of NIR absorbance improving singlet oxygen species generation among other anticancer drugs. The eminent release of DPP and adjuvant chemo-drug, Mitoxantrone from the self-assembled porphysomes is triggered by IR 775, a NIR photosensitizer upon laser irradiation. These multifunctional DPP IR Mtx @Lipo NPs have an efficient photothermal conversion efficiency of 65.8% as well as bioimaging properties. In-vitro studies in 2D and 3D models showed a significant cell death of 4T1 cells via the apoptotic pathway when irradiated with NIR laser, causing minimal damage to nearby healthy cells. DPP IR Mtx @Lipo NPs exhibited commingled PDT/PTT interdependent via NIR laser exposure, leading to mitochondrial disruption. Interestingly, the transient transfection using p53-GFP in cancer cells followed by DPP IR Mtx @Lipo NPs treatment causes rapid cell death. The activation of p53-dependent apoptosis pathways was vividly expressed, evidenced by the upregulation of Bax and increased pattern of Caspase-3 cleavage. This effect was pronounced upon transfection and induction with DPP IR Mtx @Lipo NPs, particularly in comparison to non-transfected malignant breast cancer 4T1 cells.

Melanin-Ce6-loaded polydopamine nanoparticles-based enhanced phototherapy for B16 melanoma cancer cells.

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer.

Telomerase: a nexus between cancer nanotherapy and circadian rhythm.

Cancer represents a complex disease category defined by the unregulated proliferation and dissemination of anomalous cells within the human body. According to the GLOBOCAN 2020 report, the year 2020 witnessed the diagnosis of approximately 19.3 million new cases of cancer and 10.0 million individuals succumbed to the disease. A typical cell eventually becomes cancerous because of a long-term buildup of genetic instability and replicative immortality. Telomerase is a crucial regulator of cancer progression as it induces replicative immortality. In cancer cells, telomerase inhibits apoptosis by elongating the length of the telomeric region, which usually protects the genome from shortening. Many nanoparticles are documented as being available for detecting the presence of telomerase, and many were used as delivery systems to transport drugs. Furthermore, telomere homeostasis is regulated by the circadian time-keeping machinery, leading to 24-hour rhythms in telomerase activity and TERT mRNA expression in mammals. This review provides a comprehensive discussion of various kinds of nanoparticles used in telomerase detection, inhibition, and multiple drug-related pathways, as well as enlightens an imperative association between circadian rhythm and telomerase activity from the perspective of nanoparticle-based anticancer therapeutics.

Recent Trends in Bio-nanomaterials and Non-invasive Combinatorial Approaches of Photothermal Therapy against Cancer.

In 2020, approximately 10 million deaths worldwide were attributed to cancer, making it the primary cause of death globally. Photothermal therapy (PTT) is one of the novel ways to treat and abolish cancer. PTT significantly impacts cancer theranostics compared to other therapies like surgery, chemotherapy, and radiotherapy due to its remarkable binding capability to tumor sites and lower invasiveness into normal healthy tissues. PTT relies on photothermal agents (PTAs), which generate heat by absorbing the near-infrared (NIR) light and destroying cancer cells. Several PTT agents remain longer in the reticuloendothelial system (RES) and induce toxicity, restricting their use in the biomedical field. To overcome this problem, the usage of biodegradable nano-photothermal agents is required. This review has discussed the PTT mechanism of action and different types of novel bio-nanomaterials used for PTT. We also focussed on the combinatorial effects of PTT with other cancer therapies and their effect on human health. The role of LED lights and mild hypothermia in PTT has been discussed briefly in this review.

A lipo-polymeric hybrid nanosystem with metal enhanced fluorescence for targeted imaging of metastatic breast cancer.

Cancer metastasis plays a major role in failure of therapeutic avenues against cancer. Owing to metastasis, nearly 70-80% of stage IV breast cancer patients lose their lives. Nanodrug delivery systems are playing a critical role in the therapy of metastatic cancer in the recent times. This paper reports the enhanced permeation and retention (EPR) based targeting of metastatic breast cancer using a novel nano lipo-polymeric system (PIR-Au NPs). The PIR-Au NPs demonstrated an increase in fluorescence by virtue of surface coating with gold, owing to the metal enhanced fluorescence phenomenon as reported in our earlier reports. Enhanced fluorescence of PIR-Au NPs was observed in murine mammary carcinoma cell line (4T1), as compared to free IR780 or IR780 loaded nanosystems (P-IR NPs), when incubated for same time at same concentrations, indicating its potential application for imaging and an enhanced bioavailability of IR780. Significant cell death was noted with photothermal mediated cytotoxicity in-vitro against breast cancer cells (MCF-7 and 4T1). An enhanced fluorescence was observed in the zebra fish embryos incubated with PIR-Au NPs. The enhanced permeation and retention (EPR) effect was seen with PIR-Au NPs in-vivo. A strong fluorescent signal was recorded in mice injected with PIR-Au NPs. The tumor tissue collected after 72 h, clearly showed a greater fluorescence as compared to other groups, indicating the plasmon enhanced fluorescence. We also demonstrated the EPR-based targeting of the PIR-Au NPs in-vivo by means of photothermal heat. This lipo-polymeric hybrid nanosystem could therefore be successfully applied for image-guided, passive-targeting to achieve maximum therapeutic benefits.

Glutathione - IR 797 coupled Casein Nano-Trojan for augmenting the therapeutic efficacy of camptothecin in highly invasive triple negative breast cancer.

The rapid metastasis & heterogenic constitution of triple negative breast cancer (TNBC) limits drug entry to the tumor, reducing treatment effectiveness. To address this, we have synthesized Casein nanoparticles (Cn NPs) with attached glutathione (GSH), a natural ligand for cancer cell overexpressed γ-glutamyl transpeptidase (GGT). Cn NPs encapsulated with Camptothecin and NIR dye IR 797 (CCN NPs) for combinatorial therapy of TNBC. The GSH-CCN nanoparticles (CCNG NPs) act as a Nano-Trojan to deceive the cancer cells by delivering therapeutic payloads directly to specific target cells. In this study, Casein Nano-Trojan is equipped with GSH as a targeting ligand for GGT. The binding of CCNG NPs with cell surface receptors switched the anionic charge to catanionic, prompting the target cell to engulf the nanoparticles. The Casein Nano-Trojan releases its therapeutic payload inside the target cell, potentially inhibiting proliferation & inducing a high percentage of cell death (85 ± 7 %). Disintegration of mitochondrial membrane potential, inhibition of both migration & re-growth were observed. Immunofluorescence, acridine orange/ethidium bromide stain, and nuclear fragmentation assay further confirmed the substantial DNA damage induced by the high expression of γH2AX and p53. Significant therapeutic efficacy was observed in the 3D spheroids of 4T1 cells and in vivo breast cancer mice model (BALB/c). These findings demonstrate that CCNG NPs could be an effective treatment approach for highly metastatic triple negative breast cancer.

Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.

Glioblastoma multiforme (GBM) is the most aggressive type of glioma and is often resistant to traditional therapies. Evidence suggests that glioma stem cells (GSCs) contribute to this resistance. Mithramycin (Mit-A) targets GSCs and exhibits antitumor activity in GBM by affecting transcriptional targets such as SRY-related HMG-box transcription factor 2 (SOX2), oligodendrocyte lineage transcription factor 2 (OLIG2), and zinc finger E-box binding homeobox 1 (ZEB1). However, its clinical use has been limited by toxicity. This study explored the diagnostic potential of serum extracellular vesicles (EVs) to identify Mit-A responders. Serum EVs were isolated from 70 glioma patients, and targeted gene expression was analyzed using qRT-PCR. Using chemosensitivity assay, we identified 8 Mit-A responders and 17 nonresponders among 25 glioma patients. The M-score showed a significant correlation (p = 0.045) with isocitrate dehydrogenase 1 mutation but not other clinical variables. The genes SOX2 (p = 0.005), OLIG2 (p = 0.003), and ZEB1 (p = 0.0281) were found to be upregulated in the responder EVs. SOX2 had the highest diagnostic potential (AUC = 0.875), followed by OLIG2 (AUC = 0.772) and ZEB1 (AUC = 0.632).The combined gene panel showed significant diagnostic efficacy (AUC = 0.956) through logistic regression analysis. The gene panel was further validated in the serum EVs of 45 glioma patients. These findings highlight the potential of Mit-A as a targeted therapy for high-grade glioma based on differential gene expression in serum EVs. The gene panel could serve as a diagnostic tool to predict Mit-A sensitivity, offering a promising approach for personalized treatment strategies and emphasizing the role of GSCs in therapeutic resistance.

IR-775 - Hyptis loaded bioactive nanoparticles for enhanced phyto-photothermal therapy of breast cancer cells.

Photo-responsive therapy is an emerging treatment modality due to its bioimaging and therapeutic properties. Phototherapy induces localized hyperthermia and selectively eradicates cancer cells. The current study showed that multifunctional biodegradable liposome nanosystem (HIL NPs) containing Hyptis suaveolens bioactive molecules and IR-775, a NIR dye showed efficient bioavailability to cancer ells and allowed tumor ablation upon NIR laser irradiation. The resulting entities present in the nanosystem, i.e., bioactive molecules of Hyptis, serve as an anticancer agent, and IR-775 helps in the photothermal ablation of highly metastatic breast cancer cells. Hyptis suaveolens is a weed that grows rampantly, impeding the growth of neighboring plants; nonetheless, its bioactive compounds have demonstrated therapeutic benefits. The obtained HIL NPs, photothermally active liposome nanosystem showed a high fluorescence absorption peak in the NIR range and delivered a photothermal conversion efficiency of 55.20 % upon NIR laser irradiation. TEM and particle size analyzer revealed that HIL NPs have a size of 141 ± 30 nm with a spherical shape. The results of in-ovo (zebrafish) experiments have shown efficient bioimaging capabilities with minimal concentrations of HIL NPs compared to respective controls. Furthermore, in-vitro studies of HIL NPs against triple-negative breast cancer (4T1) indicated effective anticancer activity by a combined cytotoxic effect and hyperthermia. Tumor ablation was facilitated by reactive oxygen species production and hyperthermia, leading to DNA damage and apoptosis due to overexpression of É£-H2AX, Cathepsin B, and p53, which halted cancer cell proliferation. Therefore, HIL NPs demonstrated effective anticancer effects induced by combined phyto-photothermal therapy when evaluated against an in-vitro breast cancer model.

Advances in Peptide-Decorated Targeted Drug Delivery: Exploring Therapeutic Potential and Nanocarrier Strategies.

Peptides are ideal biologicals for targeted drug delivery and have also been increasingly employed as theranostic tools in treating various diseases, including cancer, with minimal or no side effects. Owing to their receptor-specificity, peptide-mediated drug delivery aids in targeted drug delivery with better pharmacological biodistribution. Nanostructured self-assembled peptides and peptide-drug conjugates demonstrate enhanced stability and performance and captivating biological effects in comparison with conventional peptides. Moreover, they serve as valuable tools for establishing interfaces between drug carriers and biological systems, enabling the traversal of multiple biological barriers encountered by peptide-drug conjugates on their journeys to their intended targets. Peptide-based drugs play a pivotal role in the field of medicine and hold great promise for addressing a wide range of complex diseases such as cancer and autoimmune disorders. Nanotechnology has revolutionized the fields of medicine, biomedical engineering, biotechnology, and engineering sciences over the past two decades. With the help of nanotechnology, better delivery of peptides to the target site could be achieved by exploiting the small size, increased surface area, and passive targeting ability of the nanocarrier. Furthermore, nanocarriers also ensure safe delivery of the peptide moieties to the target site, protecting them from degradation. Nanobased peptide delivery systems would be of significant importance in the near future for the successful targeted and efficient delivery of peptides. This review focuses on peptide-drug conjugates and nanoparticle-mediated self-assembled peptide delivery systems in cancer therapeutics.

Trinuclear rhenium(I)-based metallocages as anticancer agents towards human cervical cancer cells.

The first examples of spherical-shaped trinuclear rhenium(I) organometallic cages displaying cytotoxic, antimetastatic, antiproliferative and DNA-damaging behavior towards a human cervical (HeLa) cancer cell line are reported. The compact design of the metallocages facilitates their interactions with biosystems leading to comparable efficiency to that of the commonly used anticancer drug cisplatin.

Destabilizing Effect of Organo Ru(II) Salts on the Intermolecular Parallel CGG Repeat DNA Quadruplex Associated with Neurodegenerative/Neuromuscular Diseases.

The cationic organo ruthenium(II) salts ([Ru(p-cymene)(ipit)(Cl)](Cl) (RuS), 1-isopropyl-3-(pyridin-2-yl)-imidazol-2-thione (ipit) and [Ru(p-cymene)(ipis)(Cl)](Cl) (RuSe), 1-isopropyl-3-(pyridin-2-yl)-imidazol-2-selenone (ipis)) are isolated, and their binding efficacy with d(CGG)15 quadruplex is investigated. Circular dichroism (CD) wavelength scan titration experiments of RuS and RuSe compounds with the intermolecular parallel quadruplex formed by d(CGG)15 (associated with neurodegenerative/neuromuscular/neuronal intranuclear inclusion disorders like FXTAS, OPMD, OPDM types 1-4, and OPML as well as FXPOI) and with the control d(CGG)15·d(CCG)15 duplex indicate their specificity toward the former. Electrophoretic mobility shift titration experiments also confirm the binding of the ligands with d(CGG)15. CD thermal denaturation experiments indicate that both RuS and RuSe destabilize the quadruplex, specifically at 10 mM concentration of the ligands. This is further confirmed by 1D 1H NMR experiments. Such a destabilizing effect of these ligands on the d(CGG)15 quadruplex indicates that RuS and RuSe chalcogen complexes can act as a template for the design of novel molecules for the diagnostics and/or therapeutics of CGG repeat expansion-associated diseases.

Toll-like receptor-immobilized carbon paste electrodes with plasma functionalized amine termination: Towards real-time electrochemical based triaging of gram-negative bacteria.

Chronic wounds caused due to bacterial biofilms are detrimental to a patient, and an immediate diagnosis of these bacteria can aid in an effective treatment, which is still an unmet clinical need. An instant and accurate identification of bacterial type could be made by utilizing the Toll-Like Receptors (TLRs) combined with Myeloid Differentiation factor 2 (MD-2). Given this, we have developed an electrochemical sensing platform to identify the gram-negative (gram-ve) bacteria using TLR4/MD-2 complex. The nonthermal plasma (NTP) technique was utilized to functionalize amine groups onto the carbon surface to fabricate cost-effective carbon paste working electrodes (CPEs). The proposed electrochemical sensor platform with a specially engineered electrochemical cell (E-Cell) identified the Escherichia coli (E. coli) in a wide linear range of 1.5×10° - 1.5×106 C.F.U./mL, accounting for a very low detection limit of 0.087 C.F.U./mL. The novel and cost-effective sensor platform identified gram-ve bacteria predominantly in a mixture of gram positive (gram+ve) bacteria and fungi. Further, towards real-time detection of bacteria and point-of-care (PoC) applications, the effect of the pond water matrix was studied, which was minimal, and the sensor could identify E. coli concentrations selectively, showing the potential application of the proposed platform towards real-time bacterial detection.