No abstract

Magnetic resonance imaging has emerged as an indispensable imaging modality for the early-stage diagnosis of many diseases. The imaging in the presence of a contrast agent is always advantageous, as it mitigates the low-sensitivity issue of the measurements and provides excellent contrast in the acquired images even in a short acquisition time. However, the stability and high relaxivity of the contrast agents remained a challenge. Here, molecules of a mononuclear, mono­(aquated), thermodynamically stable [log K MnL = 14.80(7) and pMn = 8.97] Mn­(II)-complex (1), based on a hexadentate pyridine-picolinate unit-containing ligand (H2PyDPA), were confined within a porous silica nanosphere in a noncovalent fashion to render a stable nanosystem, complex 1@SiO2NP. The entrapped complex 1 (complex 1@SiO2) exhibited r 1 = 8.46 mM–1 s–1 and r 2 = 33.15 mM–1 s–1 at pH = 7.4, 25 °C, and 1.41 T in N-(2-hydroxyethyl)­piperazine-N′-ethanesulfonic acid buffer. The values were about 2.9 times higher compared to the free (unentrapped)-complex 1 molecules. The synthesized complex 1@SiO2NP interacted significantly with albumin protein and consequently boosted both the relaxivity values to r 1 = 24.76 mM–1 s–1 and r 2 = 63.96 mM–1 s–1 at pH = 7.4, 37 °C, and 1.41 T. The kinetic inertness of the entrapped molecules was established by recognizing no appreciable change in the r 1 value upon challenging complex 1@SiO2NP with 30 and 40 times excess of Zn­(II) ions at pH 6 and 25 °C. The water molecule coordinated to the Mn­(II) ion in complex 1@SiO2 was also impervious to the physiologically relevant anions (bicarbonate, biphosphate, and citrate) and pH of the medium. Thus, it ensured the availability of the inner-coordination site of complex 1 for the coordination of water molecules in the biological media. The concentration-dependent changes in image intensities in T 1- and T 2-weighted phantom images and uptake of the nanoparticles by the HeLa cell put forward the biocompatible complex 1@SiO2NP as a potential dual-mode MRI contrast agent, an alternative to Gd­(III)-containing contrast agents.

Biomolecule-stabilized metal nanoclusters (MNCs) exhibit enormous potential as unique luminescent materials in various applications. However, synthesis of highly stable and bio-friendly fluorescent MNCs is still a challenge. Here, we report a facile synthesis of red-emitting silver nanoclusters (LYS–AgNCs) within a dithiothreitol-reduced lysozyme (LYS) scaffold. The nanoclusters exhibit a uniform size distribution, excellent water solubility, and superior photoluminescence properties featuring a quantum yield of 6.1%, a massive (280 nm) Stokes shift, and solid-state emission, and pH stability augments their applicability in dual-mode sensing platforms for Cu2+ and vitamin B12 (VB12). Two contrasting fluorescence (FL)-quenching mechanisms are responsible for the sensing; Cu2+-induced FL quenching occurs via a multifaceted mechanism involving both static and dynamic quenching, whereas the inner filter effect and Förster resonance energy transfer are mainly responsible for VB12-induced FL quenching. An inexpensive portable paper strip is fabricated using LYS–AgNCs for on-site field application, enabling instrument-free fast and visual detection of Cu2+ and VB12. Moreover, LYS–AgNCs also possess favorable biocompatibility against human cervical cancer cells (HeLa), making them a suitable nanoprobe for cell imaging and an efficient agent for detecting Cu2+ and VB12 inside live cells as well. Finally, we demonstrate the applicability of LYS–AgNCs for real-sample analysis of VB12 with a satisfactory outcome.

Metastasis is the cause of approximately 90% of cancer-related morbidities and mortalities, which is accredited to the phenomenon of EMT (epithelial to mesenchymal transition). The pathological activation of EMT during...

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/β-catenin signaling pathway molecules like β-catenin (by 0.7 fold), Gsk3β (by 0.6 fold), and pGsk-3β (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.