Towards increased selectivity of drug delivery to cancer cells: development of a LDL-based nanodelivery system for hydrophobic photosensitizers

摘要

Low-density lipoproteins (LDL), a natural iin vivo/i carrier of cholesterol in the vascular system, play a key role in thedelivery of hydrophobic photosensitizers (pts) to tumor cells in photodynamic therapy (PDT) of cancer. To make thisdelivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface bypolyethylene glycol (PEG) and dextran. Fluorescence spectroscopy and confocal fluorescence imaging were used tocharacterize redistribution of hypericin (Hyp), a natural potent pts, loaded in LDL/PEG and LDL/dextran complexes tofree LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It was shown than the redistributionprocess of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. On the otherhand, PEG does not significantly influence this process. The modification of LDL molecules by the polymers does notinhibit their recognition by cellular LDL receptors. U-87 MG cellular uptake of Hyp loaded in LDL/PEG andLDL/dextran complexes appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Itis proposed that by polymers modified LDL molecules could be used as a basis for construction of a drug transportsystem for targeted delivery of hydrophobic drugs to cancer cells expressing high level of LDL receptors.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.