Starting with a previously reported linear breast cancer targeting decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by the noncancerous cells compared to the linear peptide with two d-amino acids (x and k), and was stable toward proteolytic degradation. When immobilized on gold microcantilever surface, the cyclic peptide was able to capture breast cancer cells specifically and sense samples with ≥25 cancer cells/mL. Animal studies using mice carrying orthotopic breast MDA-MB-231 tumors showed that the cyclic peptide preferentially accumulates in tumor (2 h after injection) and is rapidly cleared from all other organs except kidneys and liver. The study highlights the discovery of a novel proteolytically stable cyclic peptide that can be used for targeted drug delivery or for enumerating circulating breast tumor cells.
Traceable poly(ethylene oxide)-poly(ester) micelles were developed through chemical conjugation of a near-infrared (NIR) dye to the poly(ester) end by click chemistry. This strategy was tried for micelles with poly(ε-caprolactone) (PCL) or poly(α-benzyl carboxylate-ε-caprolactone) (PBCL) cores. The surface of both micelles was also modified with the breast cancer targeting peptide, P18-4. The results showed the positive contribution of PBCL over PCL core on micellar thermodynamic and kinetic stability as well as accumulation in primary orthotopic MDA-MB-231 tumors within 4-96 h following intravenous administration in mice. This was in contrast to in vitro studies where better uptake of PEO-PCL versus PEO-PBCL micelles by MDA-MB-231 cells was observed. The presence of P18-4 enhanced the in vitro cell uptake and homing of both polymeric micelles in breast tumors, but only at early time points. In conclusion, the use of developed NIR labeling technique provided means for following the fate of PEO-poly(ester) based nano-carriers in live animals. Our results showed micellar stabilization through the use of PBCL over PCL cores, to have a more significant effect in enhancing the level and duration of nano-carrier accumulation in primary breast tumors than the modification of polymeric micellar surface with breast tumor targeting peptide, P18-4.
In this work, we assessed the use of confocal Raman microscopy and artificial neural network as a practical method to assess and quantify adulteration of fluid milk by addition of whey. Milk samples with added whey (from 0 to 100%) were prepared, simulating different levels of fraudulent adulteration. All analyses were carried out by direct inspection at the light microscope after depositing drops from each sample on a microscope slide and drying them at room temperature. No pre- or posttreatment (e.g., sample preparation or spectral correction) was required in the analyses. Quantitative determination of adulteration was performed through a feed-forward artificial neural network (ANN). Different ANN configurations were evaluated based on their coefficient of determination (R2) and root mean square error values, which were criteria for selecting the best predictor model. In the selected model, we observed that data from both training and validation subsets presented R2>99.99%, indicating that the combination of confocal Raman microscopy and ANN is a rapid, simple, and efficient method to quantify milk adulteration by whey. Because sample preparation and postprocessing of spectra were not required, the method has potential applications in health surveillance and food quality monitoring.
Polymeric
micellar nanoparticles represent versatile and biocompatible
platforms for targeted drug delivery. However, tracking their biodistribution,
stability, and clearance profile in vivo is challenging. The goal
of this study was to prepare surface-modified micelles with peptide
GE11 for targeting the epidermal growth factor receptor (EGFR). In
vitro fluorescence studies demonstrated significantly higher internalization
of GE11 micelles into EGFR-expressing HCT116 colon cancer cells versus
EGFR-negative SW620 cells. Azo coupling chemistry of tyrosine residues
in the peptide backbone with aryl diazonium salts was used to label
the micelles with radionuclide 64Cu for positron emission
tomography (PET) imaging. In vivo analysis of 64Cu-labeled
micelles showed prolonged blood circulation and predominant hepatobiliary
clearance. The biodistribution profile of EGFR-targeting GE11 micelles
was compared with nontargeting HW12 micelles in HCT116 tumor-bearing
mice. PET revealed increasing tumor-to-muscle ratios for both micelles
over 48 h. Accumulation of GE11-containing micelles in HCT116 tumors
was higher compared to HW12-decorated micelles. Our data suggest that
the efficacy of image-guided therapies with micellar nanoparticles
could be enhanced by active targeting, as demonstrated with cancer
biomarker EGFR.
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