Development of a new LDL-based transport system for hydrophobic/amphiphilic drug delivery to cancer cells.
Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic/amphiphilic photosensitizers to tumor cells in photodynamic therapy of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by dextran. Fluorescence spectroscopy, confocal fluorescence imaging, stopped-flow experiments and flow-cytometry were used to characterize redistribution of hypericin (Hyp), a natural occurring potent photosensitizer, loaded in LDL/dextran complex to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It is shown that the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. The modification of LDL molecules by dextran does not inhibit their recognition by cellular LDL receptors and U-87 MG cellular uptake of Hyp loaded in LDL/dextran complex appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Thus, it is proposed that dextran modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic/amphiphilic drugs to cancer cells expressing high level of LDL receptors.
Department of Biophysics, University of Pavol Jozef Safarik, Kosice, Slovak Republic.
Veronika
V
Huntosova
Diana
D
Buzova
Dana
D
Petrovajova
Peter
P
Kasak
Zuzana
Z
Nadova
Daniel
D
Jancura
Franck
F
Sureau
Pavol
P
Miskovsky
D000873:Anthracenes; D045744:Cell Line, Tumor; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*
D000873:Anthracenes; D003911:Dextrans; D004337:Drug Carriers; D008077:Lipoproteins, LDL; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin