| 초록 |
The chemically modified heparin-DOCA (HD) conjugate was previously developed as drug carriers for cancer therapy. It has a markedly lower anti-coagulant activity than heparin and can form self-assembled nanoparticles in aqueous condition. BrdU incorporation assay presents that HD conjugate can prevent cell proliferation of SCC and HUVECs. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into amphiphibilc HD conjugate through physical interactions and characterized their properties with DLS, AFM. Furthermore, the effects of HD conjugate and drug-loaded heparin nanoparticles on cytotoxicity, pharmacokinetics and anti-tumor activity were investigated. In this study, doxorubicin-loaded heparin nanoparticles designed to improve anti-tumor effect showed nano-sized particles (range of 180 to 210 nm) and high drug-loading efficiency in range of 64 to 96%, and displayed a sustained drug release pattern. In cytotoxicity, DHN 20, one of drug-loaded nanoparticles, showed the cytotoxic effect against SCC and its cytotoxic activity is similar to doxorubicin. The half life of doxorubicin could be improved by entrapping DOX into HD conjugate, demonstrating that HD conjugate contributes to the prolonged circulation time of doxorubicin in blood. In vivo studies showed that HD conjugate, DOX and DHN 20 showed a reduction in tumor mass of 42.9%, 59.8% and 73.9%, respectively, relative to that in control and DHN 20 has superior anti-tumor effects to the others. The results suggest that HD conjugate inhibits proliferation of both SCC and HUVECs and the drug-entrapped heparin nanoparticles potentially improve anti-tumor effect in SCC. |
