Back to Search
Start Over
Targeted PDT Agent Eradicates TrkC Expressing Tumors via Photodynamic Therapy (PDT)
- Source :
- Molecular Pharmaceutics; January 2015, Vol. 12 Issue: 1 p212-222, 11p
- Publication Year :
- 2015
-
Abstract
- This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for 1O2production conjugated to this structure gives 1-PDTfor photodynamic therapy. Isomeric 2-PDTdoes not bind TrkC and was used as a control throughout; similarly, TrkC– cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDTwhere only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC–-photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT(single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC– tumors, and like those of 2-PDTon TrkC+ tumors. In contrast, 1-PDTcaused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC– tumors or 2-PDTin TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n= 7) showed full tumor remission and survived until 90 days with no metastasis to key organs.
Details
- Language :
- English
- ISSN :
- 15438384 and 15438392
- Volume :
- 12
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Molecular Pharmaceutics
- Publication Type :
- Periodical
- Accession number :
- ejs34367579
- Full Text :
- https://doi.org/10.1021/mp5005564