1 research outputs found
Polyethylenimine-Dermatan Sulfate Complex, a Bioactive Biomaterial with Unique Toxicity to CD146-Positive Cancer Cells
We
report unique bioactivity of a polycation-polyanion complex
with potential utility for cancer therapy. A complex of disulfide-cross-linked
polyethylenimine (CLPEI), a polycation used for gene complexation,
and dermatan sulfate (DS), an anionic polysaccharide to shield excessive
cationic charge of the former, has toxicity to a specific group of
cancer cell lines, including B16-F10 murine melanoma, A375SM human
melanoma, and PC-3 human prostate cancer cells. These CLPEI-DS-sensitive
cells express CD146, which binds to the complex via interaction with
DS. There is a positive correlation between toxicity and intracellular
level of CLPEI, indicating that the CLPEI-DS-sensitivity is attributable
to the increased cellular uptake of CLPEI mediated by the DS-CD146
interactions. In vitro studies show that CLPEI-DS complex causes G<sub>0</sub>/G<sub>1</sub> phase arrest and apoptotic cell death. In syngeneic
and allograft models of B16-F10 melanoma, CLPEI-DS complex administered
with a subtoxic level of doxorubicin potentiates the chemotherapeutic
effect of the drug by loosening tumor tissues. Given the unique toxicity,
CLPEI-DS complex may be a useful carrier of gene or chemotherapeutics
for the therapy of CD146-positive cancers