Synthesis, in silico modelling, and in vitro biological evaluation of substituted pyrazole derivatives as potential anti-skin cancer, anti-tyrosinase, and antioxidant agents.

Twenty-five azole compounds (P1-P25) were synthesised using regioselective base-metal catalysed and microwave-assisted approaches, fully characterised by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and infrared spectra (IR) analyses, and evaluated for anticancer, anti-tyrosinase, and anti-oxidant activities in silico and in vitro. P25 exhibited potent anticancer activity against cells of four skin cancer (SC) lines, with selectivity for melanoma (A375, SK-Mel-28) or non-melanoma (A431, SCC-12) SC cells over non-cancerous HaCaT-keratinocytes. Clonogenic, scratch-wound, and immunoblotting assay data were consistent with anti-proliferative results, expression profiling therewith implicating intrinsic and extrinsic apoptosis activation. In a mushroom tyrosinase inhibition assay, P14 was most potent among the compounds (half-maximal inhibitory concentration where 50% of cells are dead, IC50 15.9 µM), with activity greater than arbutin and kojic acid. Also, P6 exhibited noteworthy free radical-scavenging activity. Furthermore, in silico docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulations predicted prominent-phenotypic actives to engage diverse cancer/hyperpigmentation-related targets with relatively high affinities. Altogether, promising early-stage hits were identified - some with multiple activities - warranting further hit-to-lead optimisation chemistry with further biological evaluations, towards identifying new skin-cancer and skin-pigmentation renormalising agents.

Blue-emissive two-component supergelator with aggregation-induced enhanced emission.

Two-component organogels offer several advantages over one-component gels, but their design is highly challenging. Hence, it is extremely important to design new approaches for the crafting of two-component organogels with interesting optical and mechanical properties. Herein, we report the design of a new class of two-component supergelators obtained from the assembly between acid functionalized tetraphenylethylene (TPE)-based dendrons and alkylated melamine. No gelation behaviour is observed for the individual components, but interestingly, remarkable gelation behaviour is observed for their hydrogen-bonded complex. The primary driving force responsible for the gelation is the strong π-π stacking interaction of TPE units. Because of the strong π-stacking of TPEs in the gel state, the C(sp2)-C(sp2) bond rotation of the TPE segment is completely arrested in the gel state, which results in intense fluorescence emission of the gels. Furthermore, excellent elastic response is observed for the gels as evident from their high storage modulus compared to loss modulus values. Our results clearly demonstrate that by the appropriate selection of the molecular components, this approach can be applied for the creation of functional nanomaterials with emergent properties absent in the individual blocks.

Phototheranostic DNA micelles from the self-assembly of DNA-BODIPY amphiphiles for the thermal ablation of cancer cells.

Design of phototheranostic agents in a single step approach is one of the challenges in cancer therapy. Herein, a one-step strategy based on amphiphilicity-driven self-assembly of DNA-BODIPY amphiphiles for the design of a new class of micelles, which offer all three phototheranostic functions, is reported. These include (i) strong emission at NIR (φf = 30%) for imaging, (ii) high photothermal conversion (η = 52%) for PTT and (iii) an ssDNA-based shell for the integration of cell targeting moieties. Selective uptake of DNA micelles into a target cancer cell and its killing by laser irradiation (635 nm) are also demonstrated. Furthermore, the excellent biocompatibility, ultrasmall nanosize and high stability of DNA micelles are promising for in vivo applications.

Efficient Capturing of Polycyclic Aromatic Micropollutants From Water Using Physically Crosslinked DNA Nanoparticles.

Design and synthesis of physically (non-covalently) cross-linked nanoparticles through host-guest interaction between ß-CD and adamantane is reported. Specific molecular recognition between ß-CD functionalized branched DNA nanostructures (host) and a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) polymer (guest) is explored for the design of the nanoparticles. The most remarkable structural features of DNA nanoparticles include their excellent biocompatibility and the possibility of various non-covalent interactions with both hydrophobic and hydrophilic organic molecules. Potential of DNA nanoparticles for the rapid and efficient capture of various micropollutants typically present in water including carcinogens (hydrophobic micropollutants), organic dyes (hydrophilic), and pharmaceutical molecules (hydrophilic) is also demonstrated. The capture of micropollutants by DNA nanoparticles is attributed to the various non-covalent interactions between DNA nanoparticles and the micropollutants. Our results clearly suggest that DNA based nanomaterials would be an ideal candidate for the capturing and removal of both hydrophilic and hydrophobic micropollutants typically present in water.

Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli.

High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule-decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.

DNA-Decorated, Helically Twisted Nanoribbons: A Scaffold for the Fabrication of One-Dimensional, Chiral, Plasmonic Nanostructures.

Crafting of chiral plasmonic nanostructures is extremely important and challenging. DNA-directed organization of nanoparticle on a chiral template is the most appealing strategy for this purpose. Herein, we report a supramolecular approach for the design of DNA-decorated, helically twisted nanoribbons through the amphiphilicity-driven self-assembly of a new class of amphiphiles derived from DNA and hexaphenylbenzene (HPB). The ribbons are self-assembled in a lamellar fashion through the hydrophobic interactions of HPB. The transfer of molecular chirality of ssDNA into the HPB core results in the bias of one of the chiral propeller conformations for HPB and induces a helical twist into the lamellar packing, and leads to the formation of DNA-wrapped nanoribbons with M-helicity. The potential of the ribbon to act as a reversible template for the 1D chiral organization of plasmonic nanomaterials through DNA hybridization is demonstrated.

Self-Assembly of an Aptamer-Decorated, DNA-Protein Hybrid Nanogel: A Biocompatible Nanocarrier for Targeted Cancer Therapy.

Nanocarrier-based chemotherapy is one of the most efficient approaches for the treatment of cancer, and hence, the design of new nanocarriers is very important. Herein, the design of a new class of physically cross-linked nanoparticles (nanogel) solely made of biomolecules including DNA, protein, and biotin as a nanocarrier for the targeted cancer therapy is reported. A specific molecular recognition interaction between biotin and streptavidin is explored for the cross-linking of a DNA nanostructure for the crafting of a nanogel. The most unique structural features of nanogels include the following: (i) excellent biocompatibility, (ii) decoration of the nanogel surface with biotin and streptavidin randomly that allowed the integration of aptamer DNA onto the surface of the nanostructure through the biotin-streptavidin interaction, (iii) high doxorubicin encapsulation efficacy through the intercalation of doxorubicin inside the DNA duplex, and (iv) stimuli responsiveness. The selective uptake of a doxorubicin-loaded nanogel by aptamer-receptor-positive cell lines (CCRF-CEM and HeLa) and its delivery inside the target cells are demonstrated. The selective uptake of the nanogel by CCRF-CEM and HeLa cells is attributed to the specific interaction between the aptamer DNA decorated on the surface of the nanogel with the PTK7 receptor overexpressed on CCRF-CEM and HeLa cell lines. These results imply that the nanogel obtained from the self-assembly of biomolecules would be ideal for the crafting of nanocarriers for targeted cargo delivery applications.

Self-assembly of DNA-tetraphenylethylene amphiphiles into DNA-grafted nanosheets as a support for the immobilization of gold nanoparticles: a recyclable catalyst with enhanced activity.

Preventing the aggregation of NPs and their recovery are the two major hurdles in NP based catalysis. Immobilization of NPs on a support has proven to be a promising strategy to overcome these difficulties. Herein we report the design of high aspect ratio two-dimensional (2D) crystalline DNA nanosheets formed from the amphiphilicity-driven self-assembly of DNA-tetraphenylethylene amphiphiles and also demonstrate the potential of DNA nanosheets for the immobilization of catalytically active NPs. The most remarkable feature of this approach is the high loading of NPs in a non-aggregated manner, and hence exhibiting enhanced catalytic activity. Recycling of NP loaded nanosheets for several cycles without reduction in catalytic efficiency by simple ultrafiltration is also demonstrated.