(775b) Targeting Cancer Cells Via Tumor-Homing Peptide Creka Conjugated Peg Hydrogel Nanoparticles
AIChE Annual Meeting
2016
2016 AIChE Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Biomaterial-Cell Interactions in Tissue Engineering
Friday, November 18, 2016 - 12:48pm to 1:06pm
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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