Targeting of Breast Cancer with Triptolide Nanoparticle
Abstract
We have demonstrated that the Triptolide (TPL) a diterpenoid tripoxides-like molecule (MW 360) purified from the herb Triptetygium wilfordii Hook F possesses a potent anti-tumor effect. To further enhance its targeting effect on tumor TPL was conjugated with human RGD and NGR that highly expressed on vessel and tumor cells and then further precessed in a liposome form as nanoparticle of RGD/NGR-PA-TPL-Liposome. The results of in vitro test RGD/NGR-PA-TPL-lipo showed a similar effect as TPL along. In the tumor bearing mice model the tail vein injection showed a good targeting effect on vessel however after 6 injections of RGD/NGR-PA-TPL-Lipo all the treated mice died of allergy (fast breathing with a pattern of IgE type immune reaction) when 7 injection was carried out indicating that the RGD/NGR is a foreign antigen to mouse. Then we decided to conjugate TPL to hyaluronan (HA) the ligand to CD44 that is highly expressed on surface of breast cancer cells. The results of in vitro and in vivo tests showed that the new nanoparticle had a similar anti-tumor effect as TPL. Conclusion: 1) in technique RGD/NGR-PA-TPL-Lipo can be obtaines; 2) human RGD/NGR enhances the targeting effect on vessel; 3) RGD/NGR acts as a foreign antigen to mouse perhaps to human too therefdre it is not a good carrier to anti-tumor toxic agent; and 4) TPL itself is potent enough to kill cancer cells without further modification.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA477044
Entities
People
- Shanmin Yang
Organizations
- University of Rochester