Blood glucose concentration and 1125 cm^-1 relative intensity.

<p>Blood glucose concentration and 1125 cm^-1 relative intensity.</p

Linearized curve-fitting parameters of blood glucose concentration and 1125 cm^-1 relative intensity from three individual mice.

<p>Linearized curve-fitting parameters of blood glucose concentration and 1125 cm^-1 relative intensity from three individual mice.</p

(A) Experimental setup: A laser beam was introduced into a microscope and focused into the selected blood vessels of live mice to collect Raman spectra.

<p>Backwards Raman scattering light from blood was projected into the entrance slit of a spectrograph. TC, temperature controller; DL, diode laser; OP, optical isolator; IF, interference filter; M, mirror; L, lens; PH, pinhole; HNF1, HNF2, holographic notch filter; CCD, charge-coupled detector; DM, dichronic mirror; BS, beam splitter; Obj, objective lens; EP, eyepiece; VC, video camera. b: Laser beam in mouse ear.</p

(A) Blood vessel in a mouse ear highlighted by dashed white lines.

<p>Scale bar is 10 μm; Fig. 5B: Raman spectra of blood with different glucose concentrations; Fig. 5C Raman spectra after normalization at a height of 1549 cm^-1.</p

Raman relative intensities of glucose (1125 cm^-1) in vivo versus the reference values with a mean absolute error of 5.7% and an Adj. R-Square of 0.91.

<p>Raman relative intensities of glucose (1125 cm^-1) in vivo versus the reference values with a mean absolute error of 5.7% and an Adj. R-Square of 0.91.</p

(A) Raman spectra of blood with different glucose concentrations; B: blood.

<p>(A) Raman spectra of blood with different glucose concentrations; B: blood.</p

Raman spectra of glucose solutions.

<p>The peaks indicative of glucose increase as function of concentration.</p

A Small Molecule Nanodrug by Self-Assembly of Dual Anticancer Drugs and Photosensitizer for Synergistic near-Infrared Cancer Theranostics

Phototherapy including photodynamic therapy (PDT) and photothermal therapy (PTT) has attracted great attention. However, applications of some photosensitizers remain an obstacle by their poor photostability. To enhance the treatment efficiency of photosensitizers and tumor theranostic effect, herein, we reported a novel carrier-free, theranostic nanodrug by self-assembly of small molecule dual anticancer drugs and photosensitizer for tumor targeting. The developed carrier-free small molecule nanodrug delivery system was formed by hydrophobic ursolic acid, paclitaxel, and amphipathic indocyanine green (ICG) associated with electrostatic, π–π stacking, and hydrophobic interactions exhibiting water stability. The self-assembling of ICG on the dual anticancer nanodrug significantly enhanced water solubility of hydrophobic anticancer drugs and ICG photostability contributing to long-term near-infrared (NIR) fluorescence imaging and effective chemophototherapy of tumor. The in vivo NIR fluorescence imaging showed that the theranostic nanodrug could be targeted to the tumor site via a potential enhanced permeability and retention effect proving the efficient accumulation of nanoparticles in the tumor site. Dramatically, chemophototherapy of tumor-bearing mice in vivo almost completely suppressed tumor growth and no tumor recurrence was observed. Encouraged by its carrier-free, prominent imaging and effective therapy, the small molecule nanodrug via self-assembly will provide a promising strategy for synergistic cancer theranostics

Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization

PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound <b>17</b> (IC₅₀ = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of <b>17</b> to PRMT5 was validated by surface plasmon resonance experiments, with a <i>K_d</i> of 0.987 μM. Kinetic experiments indicated that <b>17</b> was a SAM competitive inhibitor other than the substrate. In addition, <b>17</b> showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. <b>17</b> may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications

Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization

PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound <b>17</b> (IC₅₀ = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of <b>17</b> to PRMT5 was validated by surface plasmon resonance experiments, with a <i>K_d</i> of 0.987 μM. Kinetic experiments indicated that <b>17</b> was a SAM competitive inhibitor other than the substrate. In addition, <b>17</b> showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. <b>17</b> may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications