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.

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 greater 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.

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.

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.

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.

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.

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.

An Isothiazolanthrone-Based Self-Assembling Anticancer Color-Changing Dye for Concurrent Imaging and Monitoring of Cell Viability.

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h. Interestingly, AAT also produce differential emission inside mouse normal cells as compared to its cancer cell lines since it possess anticancer activity. The experimental observations were also validated theoretically via computational modeling.

Immunomodulatory nanosystems: An emerging strategy to combat viral infections.

The viral infection spreads with the assistance of a host. Traditional antiviral therapies cannot provide long-term immunity against emerging and drug-resistant viral infections. Immunotherapy has evolved as an efficient approach for disease prevention and treatment, which include cancer, infections, inflammatory, and immune disorders. Immunomodulatory nanosystems can dramatically enhance therapeutic outcomes by combating many therapeutic challenges, such as poor immune stimulation and off-target adverse effects. Recently, immunomodulatory nanosystems have emerged as a potent antiviral strategy to intercept viral infections effectively. This review introduces major viral infections with their primary symptoms, route of transmission & targeted organ, and different stages of the viral life cycle with respective traditional blockers. The IMNs have an exceptional capacity for precisely modulating the immune system for therapeutic applications. The nano sized immunomodulatory systems permit the immune cells to interact with infectious agents enhancing lymphatic drainage and endocytosis by the over-reactive immune cells in the infected areas. Immune cells that can be modulated upon viral infection via various immunomodulatory nanosystems have been discussed. Advancement in theranostics can yield an accurate diagnosis, adequate treatment, and real-time screening of viral infections. Nanosystem-based drug delivery can continue to thrive in diagnosing, treating, and preventing viral infections. The curative medicine for remerging and drug-resistant viruses remains challenging, though certain systems have expanded our perception and initiated a new research domain in antiviral treatments.

Insight into the Effect of Stabilizers on Anticancer and Antibacterial Activity of AgBiS2 Nanomaterial.

The near-infrared (NIR) light-absorbing AgBiS2 nanoparticles can be excited by single-wavelength light, which is the primary characteristic of a photo responsive platform. Chemical synthesis of nanomaterials inevitably requires long-chain organic surfactants or polymers to stabilize them in the nano regime. These stabilizing molecules barricade the interaction of nanomaterials with biological cells. We have produced stabilizer-free (sf-AgBiS2 ) and polymer-coated (PEG-AgBiS2 ) nanoparticles; and assessed their NIR mediated anticancer and antibacterial activity to evaluate the effect of stabilizers. sf-AgBiS2 showed better antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) and displayed excellent cytotoxicity against HeLa cells and live 3-D tumour spheroids compared to PEG-AgBiS2 both in presence and absence of NIR radiation. The photothermal therapy (PTT) results illustrated the tumour ablation ability of sf-AgBiS2 , which converted light into heat effectively up to 53.3 °C under NIR irradiation. This work demonstrates the importance of synthesizing stabilizer-free nanoparticles to produce safe and highly active PTT agents.

Lipid-coated red fluorescent carbon dots for imaging and synergistic phototherapy in breast cancer.

The synthesis of carbon dots using plant leaves is a facile and economically viable approach. Here we report the development of lipid-coated red fluorescent carbon dots (LRCDs), a biocompatible and stable nanomaterial, utilizing Clitoria ternatea leaves. The red fluorescent carbon dots (RCDs) were prepared by hydrothermal method, followed by lipid coating using rotary evaporation for imaging-guided phototherapy. RCDs generate heat in tandem with NIR laser irradiation and could therefore be employed as a photothermal agent in cancer therapy. Additionally, the fluorescent nature of RCDs can be utilized in bioimaging. The fabricated RCDs displayed a characteristic fluorescent emission maximum at 672 nm with a shoulder peak at 723 nm. Hydrophobicity is a major drawback associated with the RCDs, which limits their therapeutic efficiency due to poor biodistribution and rapid clearance. To address this limitation, we coated RCDs with soya lecithin to generate hydrophilic LRCDs with better bioavailability and therapeutic effectiveness. Further analysis using MTT assay reveals high biocompatibility and a distinct photothermal ablation potency of LRCDs against L929 and 4T1 cells, respectively. LRCDs could potentially be synthesized on a large scale and used for a variety of applications due to their low-cost, and biocompatibility.

An Easily Accessible NIR-Absorbing Tetraimide Dye and its Biotherapeutics Based Photothermal and Photodynamic Therapy.

Organic π-systems with strong absorption in the near-infrared (NIR) region are promising candidates for photothermal therapy (PTT) and photodynamic therapy (PDT). However, the synthesis of NIR π-systems involves several steps and many of them display poor photothermal conversion efficiency (PTCE). Here we present the synthesis of a tetraimide-based donor-acceptor NIR π-system, 2EHex-B having absorbance in the range of 350-900 nm. Importantly, 2EHex-B is synthesized in two steps with a 70 % high yield. Moreover, 2EHex-B shows excellent PTCE up to 50 % and good biocompatibility when encapsulated in liposomes. The liposome coated 2EHex-B, (L-2EHex-B) showed good thermal stability and efficiently kills cancer cells via PTT. Additionally, L-2EHex-B shows good reactive singlet oxygen generation ability when irradiated with a 750 nm laser. 3D cell culture model - multicellular spheroids test was performed to evaluate the efficiency of PTT. The spheroids treated with L-2EHex-B after NIR light irradiation showed increased cell death from the core of the tumor toward the periphery. The easy access to 2EHex-B makes it a potential candidate for minimally invasive cancer treatment.

Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells.

The heterogenic of TNBC and the side effects of chemo drugs lead to the failure of therapy. Protein-based nanoplatforms have emerged as an important domain in protein-engineered biomedicine for delivering anticancer therapeutics. Protein-based nanosystems are biocompatible and biodegradable, with a long half-life and high purity. TNBC is sensitive to DNA-damaging chemo drugs. In this study, we used 10-hydroxy camptothecin, which causes DNA damage in cancer cells. However, the inappropriate solubility and toxic side effects limit its application in cancer therapy. We encapsulated 10-Hydroxycamptothecin in biocompatible casein by synthesizing nanoparticles from it. The synthesized CS and CCS NPs showed excellent biocompatibility in fibroblast cell lines L929, NIH-3T3, and zebrafish embryos. Enhanced uptake of CCS NPs in zebrafish embryos and 4T1 cells, cancer cell toxicity of nearly 80-85%, sub-cellular mitochondrial localization, alterations of mitochondrial membrane potential, lysosomal localization, and reactive oxygen species generation that causes cancer cell apoptosis have been observed. Growth inhibition of 4T1 cell colonies and antimetastatic activity were also noted. Further upregulation of γ-H2AX which causes DNA damage, downregulation of the PARP protein related to DNA repair, and increased level of the CHOP protein marker for endoplasmic reticulum stress-mediated cell death were observed. The 3-D model of 4T1 cells exhibited deep tumor penetration with significant therapeutic efficacy for CCS NPs. These results imply that casein-based nanoformulation could open a new scope for safe and affordable cancer therapy in TNBC.

Label-free miniaturized electrochemical nanobiosensor triaging platform for swift identification of the bacterial type.

In chronic wounds, rapid identification of the bacterial type is critical for immediate clinical assessment. A novel, cost-effective, and label-free electrochemical nanobiosensor was developed with the help of an indigenously fabricated carbon paste working electrode to rapidly identify the bacterial type. The proposed platform made use of gold nanoparticles (AuNPs) to boost electrochemical activity, and the strong affinity of boronic acid moieties for diols allowed for detection and differentiation of gram + ve and gram -ve bacteria on the same platform. A scalable and robust miniaturized Electrochemical Cell (E-Cell) designed for the developed electrodes assisted in reducing sample waste, detection time, and Limit of Detection (LOD). Within 15 min, the proposed nano biosensing platform identified Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria with an excellent recovery rate for the blind samples. Because of its size and the extra lipopolysaccharides (LPS) layer containing diols, the bioelectrode demonstrated a superior response to E. coli, effectively distinguishing it from S. aureus. Furthermore, the proposed biosensing platform demonstrated an excellent shelf-life and reproducibility with acceptable selectivity and exhibited an excellent specificity towards bacteria, making it an ideal candidate for rapid identification of the bacterial type.

Plasma Functionalized Carbon Interfaces for Biosensor Application: Toward the Real-Time Detection of Escherichia coli O157:H7.

Nonthermal plasma, a nondestructive, fast, and highly reproducible surface functionalization technique, was used to introduce desired functional groups onto the surface of carbon powder. The primary benefit is that it is highly scalable, with a high throughput, making it easily adaptable to bulk production. The plasma functionalized carbon powder was later used to create highly specific and low-cost electrochemical biosensors. The functional groups on the carbon surface were confirmed using NH3-temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS) analysis. In addition, for biosensing applications, a novel, cost-effective, robust, and scalable electrochemical sensor platform comprising in-house-fabricated carbon paste electrodes and a miniaturized E-cell was developed. Biotin-Streptavidin was chosen as a model ligand-analyte combination to demonstrate its applicability toward biosensor application, and then, the specific identification of the target Escherchia coli O157:H7 was accomplished using an anti-E. coli O157:H7 antibody-modified electrode. The proposed biosensing platform detected E. coli O157:H7 in a broad linear range of (1 × 10-1-1 × 106) CFU/mL, with a limit of detection (LOD) of 0.1 CFU/mL. In addition, the developed plasma functionalized carbon paste electrodes demonstrated high specificity for the target E. coli O157:H7 spiked in pond water, making them ideal for real-time bacterial detection.

Impact of bandgap tuning on ZnS for degradation of environmental pollutants and disinfection.

The materials showing multiple applications are appealing for their practical use and industrial production. To realize the suitable property for various applications, we have produced ZnS (sf-ZnS) and metal-doped ZnS nanoflakes (sf-m-ZnS; where m = Cu, Ni, Cd, Bi, or Mn) and correlated their activity with bandgap variation. We obtained all these materials via hexamethyldisilazane (HMDS)-assisted synthetic method without using any surfactants, polymers, or template molecules and characterized them thoroughly using various techniques. Photocatalytic, as well as antibacterial, activities of these materials showed their bifunctional utility. We have demonstrated the effect of doping and consequent extension of absorption band to the visible region and resultant improved photocatalytic activity under sunlight. Thus, the change in bandgap influenced their performance as photocatalysts. Among all materials produced, sf-Cd-ZnS provided superior results as a photocatalyst while degrading two organic pollutants-rhodamine B (RhB) and methylene blue (MB) in water. The antibacterial activity of sf-ZnS and sf-m-ZnS against Gram-positive bacteria, i.e., Staphylococcus aureus (S. aureus), was examined by the zone of inhibition method, wherein sf-Ni-ZnS showed maximum activity. The enhanced activity of these ZnS materials can be attributed to the free surface of nanoparticles without any capping by organic molecules, which provided an intimate interaction of inorganic semiconductor material with organic and biomolecules. Thus, we have demonstrated modification of properties both by bandgap tuning of materials and providing the opportunity for intimate interaction of materials with substrates. The photocatalytic activity and antibacterial action of metal-doped ZnS produced by our method exhibited their potential for environmental remediation, specifically water purification.

The role played by bacterial infections in the onset and metastasis of cancer.

Understanding various responses of cells towards change in their external environment, presence of other species and is important in identifying and correlating the mechanisms leading to malignant transformations and cancer development. Although uncovering and comprehending the association between bacteria and cancer is highly challenging, it promises excellent perspectives and approaches for successful cancer therapy. This review introduces various bacterial species, their virulence factors, and their role in cell transformations leading to cancer (particularly gastric, oral, colon, and breast cancer). Bacterial dysbiosis permutates host cells, causes inflammation, and results in tumorigenesis. This review explored bacterial-mediated host cell transformation causing chronic inflammation, immune receptor hyperactivation/absconding immune recognition, and genomic instability. Bacterial infections downregulate E-cadherin, leading to loosening of epithelial tight junction polarity and triggers metastasis. In addition to understanding the role of bacterial infections in cancer development, we have also reviewed the application of bacteria for cancer therapy. The emergence of bacteriotherapy combined with conventional therapies led to new and effective ways of overcoming challenges associated with available treatments. This review discusses the application of bacterial minicells, microswimmers, and outer cell membrane vesicles (OMV) for drug delivery applications.