[The cytotoxic effect of a low density lipoprotein delivered aclarubicin on leukemia cells].
OBJECTIVE
To investigate the feasibility and effectiveness of low density lipoprotein (LDL) particles as a carrier of a lipophilic anthracycline drug aclarubicin (ACR) for targeting delivery to an acute monocytic leukemia cell line THP-1.


METHODS
LDL-ACR complex was prepared by incubating LDL with ACR. The intracellular ACR content was assayed fluorometrically. Cytotoxicity was studied by cell protein measurement and 3H-TdR incorporation test.


RESULTS
Intracellular accumulation of LDL-ACR was reduced when THP-1 cells were incubated in the presence of native LDL, but methylated LDL had no effect on the cellular LDL-ACR accumulation. The LDL-ACR complex caused a greater inhibition of the growth of THP-1 cells than that of normal bone marrow nucleated cells. The cellular accumulation of LDL-ACR complex was much more than that of free ACR. The 3H-TdR incorporation test showed that the complex was more effective in the inhibition of DNA synthesis than that of the free drug.


CONCLUSIONS
The potency of ACR to tumor cells increased and its toxicity to normal cells decreased when LDL was used as a carrier.
Li
W
W
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Xi
S
S
Zhang
M
M
D015250:Aclarubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000008:administration & dosage* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D008077:Lipoproteins, LDL; D015250:Aclarubicin; D004247:DNA