Targeted PDT Agent Eradicates TrkC Expressing Tumors via Photodynamic Therapy (PDT)
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- 作者：Chin Siang Kue ; Anyanee Kamkaew ; Hong Boon Lee ; Lip Yong Chung ; Lik Voon Kiew ; Kevin Burgess
- 刊名：Molecular Pharmaceutics
- 出版年：2015
- 出版时间：January 5, 2015
- 年：2015
- 卷：12
- 期：1
- 页码：212-222
- 全文大小：847K
- ISSN：1543-8392
文摘
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 1O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC鈥?cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where 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鈥?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鈥?tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC鈥?tumors or 2-PDT in 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.