Sulphur-atom positional engineering in perylenimide: structure-property relationships and H-aggregation directed type-I photodynamic therapy.

An innovative design strategy of placing sulfur (S)-atoms within the pendant functional groups and at carbonyl positions in conventional perylenimide (PNI-O) has been demonstrated to investigate the condensed state structure-property relationship and potential photodynamic therapy (PDT) application. Incorporation of simply S-atoms at the peri-functionalized perylenimide (RPNI-O) leads to an aggregation-induced enhanced emission luminogen (AIEEgen), 2-hexyl-8-(thianthren-1-yl)-1H-benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2H)-dione (API), which achieves a remarkable photoluminescence quantum yield (Φ PL) of 0.85 in aqueous environments and established novel AIE mechanisms. Additionally, substitution of the S-atom at the carbonyl position in RPNI-O leads to thioperylenimides (RPNI-S): 2-hexyl-8-phenyl-1H-benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2H)-dithione (PPIS), 8-([2,2'-bithiophen]-5-yl)-2-hexyl-1H-benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2H)-dithione (THPIS), and 2-hexyl-8-(thianthren-1-yl)-1H-benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2H)-dithion (APIS), with distinct photophysical properties (enlarged spin-orbit coupling (SOC) and Φ PL ≈ 0.00), and developed diverse potent photosensitizers (PSs). The present work provides a novel SOC enhancement mechanism via pronounced H-aggregation. Surprisingly, the lowest singlet oxygen quantum yield (Φ Δ) and theoretical calculation suggest the specific type-I PDT for RPNI-S. Interestingly, RPNI-S efficiently produces superoxide (O2˙-) due to its remarkably lower Gibbs free energy (ΔG) values (THPIS: -40.83 kcal mol-1). The non-toxic and heavy-atom free very specific thio-based PPIS and THPIS PSs showed selective and efficient PDT under normoxia, as a rare example.

Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells.

Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.

Single-cell transcriptomics reveals the intra-tumoral heterogeneity and SQSTM1/P62 and Wnt/ß-catenin mediated epithelial to mesenchymal transition and stemness of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by the complex tumor microenvironment (TME) consisting of an abundance of mesenchymal stem cells (MSCs), which is known to facilitate epithelial-to-mesenchymal transition (EMT). The development of single-cell genomics is a powerful method for defining the intricate genetic landscapes of malignancies. In this study, we have employed single-cell RNA sequencing (scRNA-seq) to dissect the intra-tumoral heterogeneity and analyze the single-cell transcriptomic landscape to detect rare consequential cell subpopulations of significance. The scRNA-seq analysis of TNBC and Normal patient derived samples revealed that EMT markers and transcription factors were most upregulated in MSC population. Further, exploration of gene expression analysis among TNBC and Normal patient-derived MSCs ascertained the role of SQSTM1/P62 and Wnt/ß-catenin in TNBC progression. Wnt/ß-catenin and Wnt/PCP signaling pathways are prominent contributors of EMT, stemness, and cancer stem cell (CSC) properties of TNBC. SQSTM1/P62 cooperates with the components of the Wnt/PCP signaling pathway and is critically involved at the interface of autophagy and EMT. Moreover, siRNA targeting SQSTM1/P62 and inhibitor of Wnt/ß-catenin (FH535) in conjunction was used to explore molecular modification of EMT and stemness markers. Although SQSTM1/P62 is not crucial for cell survival, cytotoxicity assay revealed synergistic interaction between the siRNA/inhibitor. Modulation of these important pathways helped in reduction of expression of genes and proteins contributing to CSC properties. Gene and protein expression analysis revealed the induction of EMT to MET. Moreover, co-treatment resulted in inactivation of non-canonical Wnt VANGL2-JNK signaling axis. The synergistic impact of inhibition of SQSTM1/P62 and Wnt/ß-catenin signaling facilitates the development of a potential therapeutic regimen for TNBC.

Amyloid Targeting Red Emitting AIE Dots for Diagnostic and Therapeutic Application against Alzheimer's Disease.

The emergence of neurodegenerative diseases is connected to several pathogenic factors, including metal ions, amyloidogenic proteins, and reactive oxygen species. Recent studies suggest that cytotoxicity is caused by the small, dynamic, and metastable nature of early stage oligomeric species. This work introduces a small molecule-based red-emitting probe with smart features such as increased reactivities against multiple targets, metal-free amyloid-ß (Aß), and metal-bound amyloid-ß (Aß), and most importantly, early stage oligomeric species which are associated with the most common and widespread type of dementia, Alzheimer's disease (AD). Theoretical analyses like molecular dynamics simulation and molecular docking were performed to confirm the reactivity of the molecule toward Aß and found some excellent interactions between the molecule and the peptide. The in vitro and cellular studies demonstrated that this highly biocompatible molecule effectively reduces the structural damage to mitochondria while shielding cells from apoptosis, scavenges ROS (reactive oxygen species), and attenuates multifaceted amyloid toxicity.

An in-silico approach to understand the potential role of Wnt inhibitory factor-1 (WIF-1) in the inhibition of the Wnt signalling pathway.

WIF1 (Wnt inhibitory factor 1) is a potent tumour suppressor gene which is epigenetically silenced in numerous malignancies. The associations of WIF1 protein with the Wnt pathway molecules have not been fully explored, despite their involvement in the downregulation of several malignancies. In the present study, a computational approach encompassing the expression, gene ontology analysis and pathway analysis is employed to obtain an insight into the role of the WIF1 protein. Moreover, the interaction of the WIF1 domain with the Wnt pathway molecules was carried out to ascertain the tumour-suppressive role of the domain, along with the determination of their plausible interactions. Initially, the protein-protein interaction network analysis endowed us with the Wnt ligands (such as Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt8a and Wnt9a), along with the Frizzled receptors (Fzd1 and Fzd2) and the low-density lipoprotein complex (Lrp5/6) as the foremost interactors of the protein. Further, the expression analysis of the aforementioned genes and proteins was determined using The Cancer Genome Atlas to comprehend the significance of the signalling molecules in the major cancer subtypes. Moreover, the associations of the aforementioned macromolecular entities with the WIF1 domain were explored using the molecular docking studies, whereas the dynamics and stability of the assemblage were investigated using 100 ns molecular dynamics simulations. Therefore, providing us insights into the plausible roles of WIF1 in inhibiting the Wnt pathways in various malignancies.Communicated by Ramaswamy H. Sarma.

Targeting AR-positive breast cancer cells via drug repurposing approach.

Androgen Receptor (AR) is overexpressed in almost all the molecular subtypes of breast cancer. Besides aiding the tumorigenic environment of cancer by abnormal cell proliferation, AR also takes part in promoting cancer signaling pathways, thereby promoting aggressiveness. In this study, AR was selected as the target protein in breast cancer cells. Following this, a library of 1293 FDA-approved drugs was screened via molecular docking, MD simulation, and MMPBSA binding energy. Amongst the library of compounds, Adapalene exhibited the least binding energy of (-10.2 kCal/mol) in comparison to that of the chosen reference compound, Nilutamide (-8.6 kCal/mol). Furthermore, the in vitro efficacy of Adapalene was also determined in two different breast cancer cell lines such as MCF7 (AR-positive/ER-positive) and MDA-MB-231 (AR negative/TNBC). Initially, the cell viability assay (MTT) was performed, which endowed us with a lesser IC50 value of Adapalene in comparison to Nilutamide in both cell lines. The IC50 of Adapalene was found to be 12 µM and 39.4 µM in MCF7 and MDA-MB-231 cells, respectively. Furthermore, Adapalene also induced cellular ROS and apoptosis by 3.5-fold and 26.58% in MCF7 cells. However, the overall effect of Adapalene was significantly lower in the case of MDA-MB-231 cell lines, which could be attributed to its inherent nature of the absence of hormone receptors. Conclusively, Adapalene possesses greater therapeutic efficacy in comparison to the control drug, thereby hinting towards the potential use of Adapalene in the treatment of AR-positive breast cancer.

γ-Secretase Inhibitor Potentiates the Activity of Suberoylanilide Hydroxamic Acid by Inhibiting Its Ability to Induce Epithelial to Mesenchymal Transition and Stemness via Notch Pathway Activation in Triple-Negative Breast Cancer Cells.

Histone deacetylase inhibitors, such as suberoylanilide hydroxamic acid (SAHA), possess great therapeutic value for triple-negative breast cancer patients. However, their inherent ability to induce epithelial to mesenchymal transition in various malignancies has been of greater concern. Herein, we hypothesize that SAHA facilitates epithelial to mesenchymal transition (EMT) via activation of the Notch pathway. From the literature survey, it is evident that histone deacetylase mediates the formation of the co-repressor complex upon interacting with the DNA binding domain, thereby inhibiting the transcription of the Notch downstream genes. Hence, we hypothesize that the use of SAHA facilitates the transcriptional activation of the Notch target genes, by disrupting the co-repressor complex and recruiting the coactivator complex, thereby facilitating EMT. In this study, we have observed that SAHA upregulates the expression profile of the Notch downstream proteins (such as Notch intracellular domain, Hes-1, c-Myc, etc.) and the Notch ligands (such as Jagged-1 and Jagged-2), thereby aberrantly activating the signaling pathway. Therefore, we have focused on combination therapy using a γ-secretase inhibitor LY411575 that would enhance the efficacy of SAHA by blocking the canonical Notch pathway mediated via its intracellular domain. It was observed that co-treatment significantly mediates apoptosis, generates cellular reactive oxygen species, depolarizes mitochondria, and diminishes the stemness properties. Besides, it also mediates autophagy-independent cell death and diminishes the expression of inflammatory cytokines, along with the downregulation in the expression of the Notch downstream genes and mesenchymal markers. Altogether, our study provides a mechanistic basis for combating EMT potentiated by SAHA, which could be utilized as a rational strategy for the treatment of solid tumors, especially triple-negative breast cancer.

Highly efficient color-tunable organic co-crystals unveiling polymorphism, isomerism, delayed fluorescence for optical waveguides and cell-imaging.

Photofunctional co-crystal engineering strategies based on donor-acceptor π-conjugated system facilitates expedient molecular packing, consistent morphology, and switchable optical properties, conferring synergic 'structure-property relationship' for optoelectronic and biological functions. In this work, a series of organic co-crystals were formulated using a twisted aromatic hydrocarbon (TAH) donor and three diverse planar acceptors, resulting in color-tunable solid and aggregated state emission via variable packing and through-space charge-transfer interactions. While, adjusting the strength of acceptors, a structural transformation into hybrid stacking modes ultimately results in color-specific polymorphs, a configurational cis-isomer with very high photoluminescence quantum yield. The cis-isomeric co-crystal exhibits triplet-harvesting thermally activated delayed fluorescence (TADF) characteristics, presenting a key discovery in hydrocarbon-based multicomponent systems. Further, 1D-microrod-shaped co-crystal acts as an efficient photon-transducing optical waveguides, and their excellent dispersibility in water endows efficient cellular internalization with bright cell imaging performances. These salient approaches may open more avenues for the design and applications of TAH based co-crystals.

In silico screening and identification of potential drug against p300 acetyltransferase activity in breast cancer via drug repurposing approach.

Emerging evidence portray the involvement of epigenomic reprogramming in the onset and progression of several malignancies, including breast cancer. Histone acetyltransferase (HAT) p300 is a critical epigenetic regulator that acts as a transcription co-activator and regulates various cellular processes. p300 is overexpressed in breast cancer and promotes cellular invasion and survival, making it a promising druggable target. In this study, the relevance of p300 in different cancer pathways was established. Virtual screening of the FDA-approved drug library was carried out using molecular docking, and the top 10 potential repurposed drugs were identified. Further, recalculation of binding free energy of drug-p300 complexes was carried out using molecular mechanics Poisson-Boltzmann and surface area (MM-PBSA) method after molecular dynamic simulation. Based on molecular dynamic simulation parameters and binding free energy analysis, two drugs, namely Netarsudil (-305.068 kJ/mol) and Imatinib (-260.457 kJ/mol), were identified as potential repurposed drugs to inhibit the activity of p300. In conclusion, these findings suggest, Netarsudil and Imatinib might be a potential repurposed drug to combat breast cancer via p300 inhibition.Communicated by Ramaswamy H. Sarma.

Understanding Deformation and Breakup Tendency of Shear-Thinning Viscoelastic Drops in Constricted Microchannels.

The study of drop deformation in response to various stresses has long piqued the interest of several academics. The deformation behavior of cells, drug carriers, and even drug particles moving via microcapillaries inside the human body can be modeled using a viscoelastic drop model. A drop breakup study can also provide better design guidance for nanocarriers that can deliver on-demand burst drug releases at specific cancer sites. Thus, we attempted to investigate the deformation and breakup of a shear-thinning finitely extensible nonlinear elastic-peterlin (FENE-P) drop moving through the constricted microchannel. The computational simulation suggested that drop deformation and breakup can be manipulated by varying of parameters like channel confinement, Deborah number, solvent viscosity ratio, viscosity ratio, and capillary number. We attempted to find the critical capillary number for initiation of drop breakup. Observations from present study will give valuable insights into deformation and breakup patterns of drug carriers inside constricted microcapillaries. The simulations of the two-phase viscoelastic drop─Newtonian matrix system were performed on an open-source solver, Basilisk.

The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.

The Notch pathway is remarkably simple without the interventions of secondary messengers. It possesses a unique receptor-ligand interaction that imparts signaling upon cleavage of the receptor followed by the nuclear localization of its cleaved intracellular domain. It is found that the transcriptional regulator of the Notch pathway lies at the intersection of multiple signaling pathways that enhance the aggressiveness of cancer. The preclinical and clinical evidence supports the pro-oncogenic function of Notch signaling in various tumor subtypes. Owing to its oncogenic role, the Notch signaling pathway assists in enhanced tumorigenesis by facilitating angiogenesis, drug resistance, epithelial to mesenchymal transition, etc., which is also attributed to the poor outcome in patients. Therefore, it is extremely vital to discover a suitable inhibitor to downregulate the signal-transducing ability of Notch. The Notch inhibitory agents, such as receptor decoys, protease (ADAM and γ-secretase) inhibitors, and monoclonal/bispecific antibodies, are being investigated as candidate therapeutic agents. Studies conducted by our group exemplify the promising results in ablating tumorigenic aggressiveness by inhibiting the constituents of the Notch pathway. This review deals with the detailed mechanism of the Notch pathways and their implications in various malignancies. It also bestows us with the recent therapeutic advances concerning Notch signaling in the context of monotherapy and combination therapy.

Engineered Hybrid Nanosystem for Homologous Targeting of EMT Induced Triple Negative Breast Cancer Cells.

The increased mortality rate due to metastatic breast cancer with poor prognosis has raised concern over its effective therapy. Though various therapies and anticancer drugs have been approved, there is still a lack in the targeting of metastatic triple negative breast cancer (TNBC). We have developed a hybrid nanosystem that was synthesized by fusing exosomes from MCF-7 cells and nanovesicles from the MDA MB-231 cells that would be targeted. The developed nanosystem was characterized by various techniques like Western blotting, AFM, FETEM, DLS, CD, and fluorescence spectroscopy. The hybrid system was used for the delivery of an HDAC inhibitor, Trichostatin A (TSA), in combination with lapatinib (a tyrosine kinase inhibitor) for cotherapy of epithelial to mesenchymal transition (EMT) induced TNBC. This targeted cotherapy module had higher efficiency and effectivity in the reduction of metastatic ability and proliferation of EMT induced MDA MB-231 cells as compared to free inhibitor treatment or untargeted cotherapy. Reduction in the expression of the Wnt/ß-catenin signaling pathway molecules like ß-catenin (by 0.7 fold), Gsk3ß (by 0.6 fold), and pGsk-3ß (0.3 fold) was observed upon treatment. This subsequently resulted in the suppression of EMT markers, thereby resulting in reversing EMT to MET and suppressing metastatic breast cancer.

Living Gut Bacteria Functionalized with Gold Nanoclusters and Drug for Facile Cancer Theranostics.

Bacbots are potent self-propelling vehicles for targeted therapy that can be guided by chemical and biochemical stimuli of the host. In addition, they can be guided externally by the use of magnetic field or other physical forces. The challenge is to incorporate drugs and diagnostic tools in living bacteria with retention of theranostic activity until reaching the targets and easy clearance of the remainder following the treatment. We report that living Lactobacillus rhamnosus, when functionalized with photoluminescent Au nanoclusters and the anticancer drug methotrexate, was cytotoxic to monolayer and spheroids of cancer cells (HeLa and HT29) even at a low dose of bacteria used (107 cfu/mL). The observed cell death was nearly 90% in HeLa spheroids and 70% in HT29 spheroids. Further, functionalization of the bacterial surface with the nanoclusters helped incorporate the drug onto their cell surfaces. The drug and nanocluster-loaded bacteria annihilated the cells and the spheroids in a rather short time (6 h) that revealed the specificity and effectiveness of the bacbots. The bacbots exhibited synergistic toxicity on the cells as their effect was more than the drug and the bacteria individually. This higher toxicity could be associated with elevated levels of reactive oxygen species generated in the bacbot-treated cells. The multifunctional bacbots reported here provide an option for guided therapy with the natural variant of the human gut-friendly living bacteria without the need for attenuation or genetic modification.

Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques.

Governing protein-protein interaction networks are the cynosure of cell signaling and oncogenic networks. Multifarious processes when aligned with one another can result in a dysregulated output which can result in cancer progression. In the current research, one such network of proteins comprising VANG1/SCRIB/NOS1AP, which is responsible for cell migration, is targeted. The proteins are modeled using in-silico approaches, and the interaction is visualized utilizing protein-protein docking. Designing drugs for the convoluted protein network can serve as a challenging task that can be overcome by fragment-based drug designing, a recent game-changer in the computational drug discovery strategy for protein interaction networks. The model is exposed to the extraction of hotspots, also known as the restrained regions for small molecular hits. The hotspot regions are subjected to a library of generated fragments, which are then recombined and rejoined to develop small molecular disruptors of the macromolecular assemblage. Rapid screening methods using pharmacokinetic tools and 2D interaction studies resulted in four molecules that could serve the purpose of a disruptor. The final validation is executed by long-range simulations of 100 ns and exploring the stability of the complex using several parameters leading to the emergence of two novel molecules VNS003 and VNS005 that could be used as the disruptors of the protein assembly VANG1/SCRIB/NOS1AP. Also, the molecules were explored as single protein targets approbated via molecular docking and 100 ns molecular dynamics simulation. This concluded VNS003 as the most suitable inhibitor module capable of acting as a disruptor of a macromolecular assembly as well as acting on individual protein chains, thus leading to the primary hindrance in the formation of the protein interaction complex.

Multi-targeting TACE/ADAM17 and gamma-secretase of notch signalling pathway in TNBC via drug repurposing approach using Lomitapide.

The aberrant expression of the Notch signalling pathway genes aids in potentiating the belligerent characteristics of numerous malignancies. Besides imparting abnormal proliferation and metastasis, the Notch also aids in the metabolic reprogramming of tumor cells. Since the activation of the Notch pathway is mediated via TACE/ADAM protease and the γ-secretase complex, hence it is crucial in determining a multi-targeted therapeutic approach to target these major proteases to downregulate the aberrant Notch signalling pathway. In this study, Lomitapide was chosen based on its binding score (-305.108 kJ/mol and - 173.174 kJ/mol) against the crucial proteases, TACE and γ-secretase, respectively. Further, the remarkable antitumor properties of Lomitapide were established on the TNBC cell lines (MDA-MB-231 and MDA-MB-468), along with the EMT-induced MDA-MB-468 cells. Apart from inducing ∼2 to 2.5-fold increase in the cellular ROS levels, Lomitapide treatment induced significant apoptosis, arrested cell cycle progression and reduced sphere and colony forming abilities of the TNBC cells. Differentiated epithelial phenotype with diminished CD44-stem cell marker was also observed upon treatment. Furthermore, reduction of migration potential, decrease in the gene expression profile of the EMT markers, along with downregulation of the Notch signalling genes were evident in the treated TNBC cells. Altogether, the present study attributes the repurposing of Lomitapide as an effective therapeutic agent against the major proteases of the Notch pathway to combat TNBC progression and dissemination.

Mannosylated Gold Nanoclusters Incorporated with a Repurposed Antihistamine Drug Promethazine for Antibacterial and Antibiofilm Applications.

Drug repurposing presents a workable strategy in tackling antibiotic resistance. Many known drugs have been repurposed for their applications against different targets. Antihistamines that are usually used to treat allergy symptoms can be combined with nanoscale materials to enhance their efficiency. Herein, we explored the antimicrobial properties of a common antihistamine drug, promethazine, in Gram-positive and Gram-negative bacteria. Being positively charged, promethazine was easily incorporated into the mannose-conjugated bovine serum albumin-stabilized promethazine hydrochloride gold nanoclusters. Capping with d-mannose helped in targeting the bacteria by inhibiting their adhesive appendage called pili. Following their uptake, drugs released inside the bacteria caused reactive oxygen species production and membrane permeability alteration, ultimately resulting in bacterial inhibition. Additionally, they were also explored for biofilm eradication. As observed through staining assays, the number of dead cells increased with increasing concentration of drug-loaded gold nanoclusters in the biofilm mass. Therefore, the as-synthesized mannosylated gold nanoclusters incorporated with promethazine were analyzed for potential antibacterial and antibiofilm applications.

A photo-responsive fluorescent amphiphile for target-specific and image-guided drug delivery applications.

Multifunctional drug delivery systems are the centerpiece of effective chemotherapeutic strategies. Herein, we report the synthesis of an acetazolamide-linked cyanine-3-based NIR-responsive fluorescent macrocyclic amphiphile that self-assembled into spherical nanostructures in the aqueous medium via a J-aggregation pattern. The amphiphile shows various favorable properties of lipids. The photocleavage of the strained dioxacycloundecine ring induces spherical to nanotubular self-assembly with concomitant release of an encapsulated anticancer drug, doxorubicin (Dox), in a controlled manner. The CA-IX targeted amphiphile also showed lower cytotoxicity, effective cellular uptake, and Dox delivery to the model carcinoma cells.

In Vitro Therapeutic Attributes of Luminescent Hydroxyapatite Nanoparticles in Codelivery Module.

Imminent prospects of clinical importance have been accomplished through divergent treatment modalities implemented using nanoscale platforms. In the present study, hydroxyapatite nanoparticles doped with copper nanoclusters (HAPs) were explored for codelivery of a hydrophobic drug, namely, norfloxacin (NX), and a hydrophilic photosensitizer, such as methylene blue (MB). NX and MB were successfully homed into HAPs (MB-NX-HAPs), which further exhibited a pH-dependent release of both. With the objective of attaining an enhanced effect, MB-NX-HAPs were evaluated for combination therapy, involving chemotherapy and photodynamic therapy (PDT) with irradiation at 640 nm. The combinatorial therapy approach was initially applied for antibacterial therapy, which suggested a considerable reduction in bacterial growth of Gram-negative strain Pseudomonas aeruginosa MTCC 2488. Thereafter, the antiproliferative study performed in cancer cell lines (HeLa and MCF-7) revealed the efficiency of MB-NX-HAPs in bestowing a combinatorial effect through chemotherapy and PDT (irradiation at 640 nm). The combined effect exerted through MB-NX-HAPs subsequently induced reactive oxygen species (ROS) generation, cell cycle alteration, and apoptosis activation in cancer cells. The biocompatible nature of MB-NX-HAPs was appreciably shown through their minimal effect on the normal cell line (HEK-293). Additionally, HAPs through luminescence of copper nanoclusters were suggested to aid in bioimaging of cancer cell lines.

Hierarchical Passage of Gold Nanoclusters in Living Bacteria.

Gold (Au) nanoclusters chemically synthesized on the cell surface of living Lactobacillus rhamnosus rendered them photoluminescent. Importantly, the bacteria were viable and the clusters were passed down the generations with the loss of luminescence in the first subculture onward. The clusters were agglomerated into spherical structures of 100-200 nm, without being converted to plasmonic Au nanoparticles, on the cell surfaces of the bacteria of all six subcultures studied. The results indicated the role of cell wall remodeling in transforming the Au nanoclusters into larger aggregates down the generations. This may hold important implications for using nanoparticle-studded bacteria in theranostics.

Proline selective labeling via on-site construction of naphthoxazole (NapOx).

Chemoselective construction of naphthoxazoles (NapOx) via a three-component annulation reaction enables proline selective labeling of peptides in solution or in solid-phase synthesis. The fluorogenic peptides possess low cytotoxicity, efficient cell membrane permeability and excellent bioimaging potential for biomedical applications.