467292 Targeting Cancer Cells Via Tumor-Homing Peptide Creka Conjugated Peg Hydrogel Nanoparticles
Targeting cell microenvironment via nano-particle based therapies holds great promise for treatment of various diseases. One of the main challenges in targeted delivery of nanoparticles for cancer therapy includes reduced localization of delivery vehicles at tumor site. The therapeutic efficacy of drugs can be improved by recruiting delivery vehicles towards specific region of tumorigenesis in the body. Here, we demonstrate an effective approach in creating PEG particles via water-in-water emulsion technique where tumor-homing peptide CREKA was used for functionalization. Simultaneous conjugation of laminin peptide IKVAV into hydrogel network and influence of altered combinations of ligands on intracellular uptake of anticancer drugs by HeLa cells were investigated. Synthesis of peptide coupled PEG hydrogel nanoparticles were confirmed by Fourier Transform Infrared Spectrometer (FTIR) and X-ray fluorescence spectroscopy (XRF). Size and morphology of nanoparticles were characterized by field emission scanning electron microscopy (FESEM), Atomic Force Microscope (AFM) and dynamic light scattering (DLS). FESEM micrograph and hydrodynamic radius measurements demonstrated that the majority of particles were in sub-micron scale (Figure 1A and 1B). CREKA conjugated hydrogel nanoparticles were more effective to improve apoptotic effects of the model drug Doxorubicin (DOX) compared to that of particles conjugated with other peptides. Fluorescence intensity analysis on confocal micrographs suggested significantly higher cellular uptake of CREKA conjugated PEG particles than internalization of nanoparticles in other groups (Figure 1C). We observed that fibrin binding ability of PEG particles could be increased up to 94% through CREKA conjugation. Our results suggest the possibility of cancer cell targeting via CREKA-functional PEG nanoparticles.
Figure 1: A) FESEM micrograph of PEG hydrogel nanoparticles (scale bar =200 nm). B) Size distribution of PEG nanonanoparticles were obtained via dynamic light scattering. C) Cellular internalization of DOX-loaded PEG hydrogel nanoparticles and the tumor-homing peptide coupled PEG hydrogel nanoparticles visualized by laser scanning confocal microscope. First row illustrates cell nuclei staining with DAPI (blue); middle raw DOX fluorescence and the third row shows the merged channels (scale bar =10 µm).
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