Abstract
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 G0/G1 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.
| Original language | English |
|---|---|
| Pages (from-to) | 990-999 |
| Number of pages | 10 |
| Journal | ACS Biomaterials Science and Engineering |
| Volume | 3 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2017 Jun 12 |
| Externally published | Yes |
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Keywords
- bioactive biomaterials
- CD146
- dermatan sulfate
- melanoma
- polyethylenimine
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
Cite this
Polyethylenimine-Dermatan Sulfate Complex, a Bioactive Biomaterial with Unique Toxicity to CD146-Positive Cancer Cells. / Kim, Bieong Kil; Kim, Dongkyu; Kwak, Gijung; Yhee, Ji Young; Kwon, Ick Chan; Kim, Sun Hwa; Yeo, Yoon.
In: ACS Biomaterials Science and Engineering, Vol. 3, No. 6, 12.06.2017, p. 990-999.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polyethylenimine-Dermatan Sulfate Complex, a Bioactive Biomaterial with Unique Toxicity to CD146-Positive Cancer Cells
AU - Kim, Bieong Kil
AU - Kim, Dongkyu
AU - Kwak, Gijung
AU - Yhee, Ji Young
AU - Kwon, Ick Chan
AU - Kim, Sun Hwa
AU - Yeo, Yoon
PY - 2017/6/12
Y1 - 2017/6/12
N2 - 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 G0/G1 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.
AB - 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 G0/G1 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.
KW - bioactive biomaterials
KW - CD146
KW - dermatan sulfate
KW - melanoma
KW - polyethylenimine
UR - http://www.scopus.com/inward/record.url?scp=85020703733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020703733&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.7b00207
DO - 10.1021/acsbiomaterials.7b00207
M3 - Article
AN - SCOPUS:85020703733
VL - 3
SP - 990
EP - 999
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
SN - 2373-9878
IS - 6
ER -