DataSheet1_Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer.pdf

Chemotherapy is one of the main treatments for colorectal cancer, but systemic toxicity severely limits its clinical use. Packaging hydrophobic chemotherapeutic drugs in targeted nanoparticles greatly improve their efficacy and reduce side effects. We previously identified a novel colorectal cancer specific binding peptide P-LPK (LPKTVSSDMSLN) from phage display peptide library. Here we designed a self-assembled paclitaxel (PTX)-loaded nanoparticle (LPK-PTX NPs). LPK-PTX NPs displayed a superior intracellular internalization and improved tumor cytotoxicity in vitro. Cy5.5-labeled LPK-PTX NPs showed much higher tumor accumulation in colorectal cancer-bearing mice. Furthermore, LPK-PTX NPs exhibit enhanced antitumor activity and decreased systemic toxicity in colorectal cancer patient-derived xenografts (PDX) model. The excellent in vitro and in vivo antitumor efficacy proves the improved targeting drug delivery, suggesting that peptide P-LPK has potential to provide a novel approach for enhanced drug delivery with negligible systemic toxicity.</p

Cytotoxic 4-phenylcoumarins from the flowering buds of <i>Mesua ferrea</i>

Eleven 4-phenylcoumarins including three new 4-phenylcoumarins, mesuaferols A–C (1–3), together with eight known 4-phenylcoumarins (4–11) have been isolated from the flowering buds of Mesua ferrea. Their structures were elucidated via UV, IR, HR-ESI-MS, and NMR spectral data. Compound 9 showed moderate cytotoxic activity toward MDA-MB-231, MCF-7, HepG2 and HeLa cell lines with IC50 values of 13.68 ± 1.36 μM, 9.27 ± 1.84 μM, 21.06 ± 1.95 μM, and 7.26 ± 1.68 μM, respectively, and other compounds showed weak cytotoxicity.</p

<i>In Vitro</i> Functional Quality Characterization of NOTA-Modified Somatropins

Chemical modifications on protein biopharmaceuticals introduce extra variability in addition to their inherent complexity, hence require more comprehensive analytical and functional characterization during their discovery, development, and manufacturing. Somatropin (i.e., recombinant human growth hormone, rhGH) modified with the chelating agent <i>S</i>-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) allows the incorporation of radiometals for research and possible theranostic purposes. We previously demonstrated that this conjugation leads to multiple substitution degrees and positional isomers within the product. <i>In vitro</i> techniques at the molecular and cellular levels were now applied to assess their functional quality: (i) size exclusion chromatography (SEC) demonstrated functional complexation with human growth hormone binding protein (hGHBp) to the different NOTA-modified somatropins as well as to gallium chelated NOTA-functionalities (Ga-10:1 NOTA–somatropin); (ii) native mass spectrometry (MS) offered in-depth information, a substitution degree up to four NOTAs was still functional; (iii) circular dichroism (CD) analysis confirmed the complexation of unmodified and NOTA-modified somatropin to hGHBp; and (iv) a hGHR bioassay demonstrated initiation of the signal transduction cascade, after binding of all investigated products to the receptor presented on cells with a similar potency (pEC₅₀ values between 9.53 and 9.78) and efficacy (<i>E</i>_max values between 130 and 160%). We conclude that the NOTA-modified somatropins do not possess a significantly different <i>in vitro</i> functionality profile compared to unmodified somatropin. Techniques such as SEC, MS, and CD, traditionally used in the physicochemical characterization of proteins have a demonstrated potential use in the functionality evaluation not only in drug discovery and development but also in quality control settings

Additional file 1 of Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial

Additional file 1. Protocol for the prevention of infections