Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).
Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).
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DOI：
10.1021/mp5005564
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发表时间：
2015-01-05
影响因子：
4.9
通讯作者：
Burgess K
中科院分区：
文献类型：
--
作者：
Kue CS;Kamkaew A;Lee HB;Chung LY;Kiew LV;Burgess K
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– 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–-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-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC– 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.
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影响因子：
37.3
作者：
Bhuvaneswari R;Gan YY;Soo KC;Olivo M
通讯作者：
Olivo M
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
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作者：
Chou YS;Chang CC;Chang TC;Yang TL;Young TH;Lou PJ
通讯作者：
Lou PJ
影响因子：
46.2
作者：
Kamkaew A;Lim SH;Lee HB;Kiew LV;Chung LY;Burgess K
通讯作者：
Burgess K
影响因子：
6.4
作者：
Borsi, L;Balza, E;Zardi, L
通讯作者：
Zardi, L