Synergistic Effect of Photothermally Targeted NIR-Responsive Nanomedicine-Induced Immunogenic Cell Death for Effective Triple Negative Breast Cancer Therapy.

Triple negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have approved targeted therapy. Therefore, patients primarily depend on forceful systemic chemotherapy that has unavoidable harmful side effects, resulting in inadequate therapeutic outcomes and leading to a high mortality rate. Hence, there is an urgent need to develop targeted therapies for the TNBC populace. Developing a new nanotherapeutic approach of combinational therapy could be an effective alternative strategy. Therefore, we designed a combination of hyaluronan (HA)-polyaniline (PANi)-imiquimod (R837), denoted as HA-PANi/R837, nanoparticles (NPs) that exhibited a high extinction coefficient of 8.23 × 108 M-1 cm-1 and adequate photothermal conversion efficiency (PCE) (η = 41.6%), making them an efficient photothermal agent (PTA) that is highly beneficial for selective CD44-mediated photothermal ablation of TNBC tumors. Furthermore, co-encapsulation of R837 (toll-like receptor 7 agonist) immunoadjuvant molecules triggers an immune response against the tumor. The formed CD44-targeted HA-PANi/R837 NPs' selectivity incinerates the tumor under near-infrared (NIR)-triggered photothermal ablation, generating tumor-associated antigens and triggering R837 combination with anti-CTLA-4 for immunogenic cell death (ICD) activation to kill the remaining tumor cells in mice and protect against tumor relapse and metastasis. Our results demonstrated that novel HA-PANi/R837 NP-induced photothermal ICD achieved in CD44-targeted TNBC is a promising application.

Novel Quinoline-Based Thiazole Derivatives for Selective Detection of Fe3+, Fe2+, and Cu2+ Ions.

New quinoline-based thiazole derivatives QPT and QBT were synthesized and characterized by various spectroscopic and single-crystal X-ray crystallographic studies. The metal-sensing properties of the probes were further examined by absorption and fluorescence spectrometry. The fluorescence intensity of QPT and QBT was remarkably quenched during the addition of Fe3+, Fe2+, and Cu2+ ions in THF/H2O (1:1) at pH = 7.4 in HEPES buffer, while the addition of other metal ions did not affect the fluorescence intensity of the ligands. The detection ability of the probes QPT and QBT was further investigated by titration with various equivalents of metal ions, optimized pH ranges for detection, and reversibility with Na2EDTA for biological applications.

Application of real sample analysis and biosensing: Synthesis of new naphthyl derived chemosensor for detection of Al3+ ions.

A new chemosensor (NANH) based on naphthyl moiety was synthesized with good selectivity and sensitivity towards Al3+ ions via the inhibition by operating through dual mechanisms like photo-induced electron transfer (PET) and excited-state intramolecular proton transfer (ESIPT). The synthesized NANH was validated by various techniques such as 1H, 13C NMR and mass spectrum. While prominent fluorescent enhancement was observed from the NANH upon binding with Al3+ ions, however, other metal ions have not responded in the emission spectrum. Detection limit and association constant of NANH for Al3+ were calculated as 1.2 × 10-7 M and 4.09 × 104 M-1 by using fluorescence titration method. Binding ratio (1:1) of NANH with Al3+ ions were proved by Job's plot and DFT studies. Furthermore, aluminium in variety of water samples was determined, and NANH could be used for biosensing of Al3+ in living cells.

A novel 8-nitro quinoline-thiosemicarbazone analogues induces G1/S & G2/M phase cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway.

A series of novel 8-nitro quinoline-based thiosemicarbazone analogues were synthesized and characterized by various spectroscopic and single crystal X-ray analyses. The potent antitumor effects of synthesized compounds towards the cancer cells were evaluated by MTT assay. Amongst, the compound 3a exhibited the highest inhibitory activity and the compounds 3f and 3b were also showed significant activity. The molecular mechanistic studies of cell death have demonstrated that the treated potent compound 3a induced G1/S & G2/M phase cell cycle arrest and induced apoptosis via mitochondrial dysfunction and increased the production of cytotoxic ROS levels. The RT-PCR gene expression analysis revealed that the cell death induced by activation of caspase-3 dependent intrinsic apoptotic signaling pathway. Further, the molecular binding affinity of compounds with estrogen receptor alpha was calculated by molecular docking studies. Thus, novel 8-nitro quinoline-thiosemicarbazone analogues provide a unique tool for breast cancer therapeutic tactics.

Synthesis and X-ray study of dispiro 8-nitroquinolone analogues and their cytotoxic properties against human cervical cancer HeLa cells.

A series of unique dispiro analogues containing an oxindole pyrrolidine 8-nitroquinolone hybrid has been obtained through a one-pot three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and benzylamine with (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones. The structures of the newly synthesized compounds were characterized by using different spectroscopic techniques and by X-ray diffraction studies of their regio- and stereochemistry. All the synthesized compounds were screened for in vitro cytotoxic activity against the human cervical cancer cell line HeLa. The compounds have exhibited potent inhibition against human cervical cancer cells and insignificant toxicity to normal cells. The compounds 6d, 6a, 6h, 6b, and 6e induced apoptosis of HeLa cells, through ROS influx. The expression levels of proteins involved in the mitochondrion-related pathways were detected, and Western blot analysis showed that apoptosis occurred via activation of caspase-3.

An efficient new dual fluorescent pyrene based chemosensor for the detection of bismuth (III) and aluminium (III) ions and its applications in bio-imaging.

A new simple pyrene based schiff base chemosensor 1 (nicotinic acid pyren-1-ylmethylene-hydrazide) has been constructed and is prepared from 1-pyrenecarboxaldehyde and nicotinic hydrazide. Notably, the chemosensor 1 exhibited remarkable colour changes while in the presence of trivalent metal ions like Bi3+ & Al3+ ion in DMSO-H2O, (1:1 v/v, HEPES = 50 mM, pH = 7.4). The UV-Vis spectral investigation of chemosensor 1 showed that the maximum absorption peak appeared at 378 nm. In emission studies, chemosensor 1 develops weak fluorescence, while upon the addition of Bi3+ and Al3+ ions, it exhibits an enhancement of fluorescence intensity. Nevertheless, rest of metal ions have no changes in the emission spectra. The association constant of chemosensor 1 for binding to Bi3+ & Al3+ system had a value of 1.27 × 104 M-1 and 1.53 × 104 M-1. The detection limits were 0.12 µM for Bi3+ and 0.17 µM for Al3+ respectively. The overall results reveal that chemosensor 1 can act as a dual-channel, highly selective, and sensitive probe for Bi3+ and Al3+ ions. Moreover, the fluorescence imaging of chemosensor 1 was applied in RAW 264.7 cell line and cytotoxicity assay prove that this chemosensor 1 is non-toxic as well as highly biocompatible.

Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions.