Vascular targeting to the SST2 receptor improves the therapeutic response to near-IR two-photon activated PDT for deep-tissue cancer treatment.
Vascular targeting to the SST2 receptor improves the therapeutic response to near-IR two-photon activated PDT for deep-tissue cancer treatment.
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DOI：
10.1016/j.bbagen.2013.05.043
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发表时间：
2013-10
影响因子：
3
通讯作者：
Rebane, Aleksander K.
中科院分区：
文献类型：
--
作者：
Starkey, Jean R.;Pascucci, Elizabeth M.;Drobizhev, Mikhail A.;Elliott, Aleisha;Rebane, Aleksander K.
光动力疗法的更广泛的临床接受目前受到以下因素的阻碍：（a）较差的深度功效，和（B）在治疗期间倾向于建立血管生成环境。正在通过利用NIR组织透明窗口和通过使用双光子吸收（2 PA）的光激活来寻求改进的深度功效。在这里，我们使用PDT敏化剂的双光子激活，非靶向，靶向SST 2受体或EGF受体，以实现深层组织治疗。使用SST 2 r表达阳性或阴性的人肿瘤系，以及鼠3LL细胞和牛主动脉内皮细胞。在体外和冷冻异种移植切片中评价癌细胞和肿瘤脉管系统上SST 2受体的表达。PDT对肿瘤血流的作用在静脉内注射FITC结合的葡聚糖150 K后使用体内扫描进行跟踪。PDT疗效对激光脉冲持续时间的依赖性进行了评价。将靶向血管SST 2受体的有效性与EGF受体或无靶向的有效性进行比较。即使在来自SST 2受体阴性细胞系的肿瘤中，肿瘤血管也对SST 2受体染色，而SST 2 r靶向PDT导致肿瘤血管关闭。将脉冲从~120 fs拉伸到~3 ps导致PDT功效的损失，尤其是在更大的深度处。靶向SST 2受体的PDT比非靶向PDT或靶向EGF受体的PDT有效得多。使用奥曲肽靶向肿瘤血管上表达的SST 2受体是PDT的一种极好方法，复发率低，一些长期治愈。
Broader clinical acceptance of photodynamic therapy is currently hindered by (a) poor depth efficacy, and (b) predisposition towards establishment of an angiogenic environment during the treatment. Improved depth efficacy is being sought by exploiting the NIR tissue transparency window and by photo-activation using two-photon absorption (2PA). Here, we use two photon activation of PDT sensitizers, untargeted, targeted to SST2 receptors or EGF receptors, to achieve deep tissue treatment. Human tumor lines, positive or negative for SST2r expression were used, as well as murine 3LL cells and bovine aortic endothelial cells. Expression of SST2 receptors on cancer cells and tumor vasculature was evaluated in vitro and frozen xenograft sections. PDT effects on tumor blood flow were followed using in vivo scanning after intravenous injection of FITC conjugated dextran 150K. Dependence of the PDT efficacy on the laser pulse duration was evaluated. Effectiveness of targeting to vascular SST2 receptors was compared to that of EGF receptors, or no targeting. Tumor vasculature stained for SST2 receptors even in tumors from SST2 receptor negative cell lines, and SST2r targeted PDT led to tumor vascular shutdown. Stretching the pulse from ~120 fs to ~3 ps led to loss of the PDT efficacy especially at greater depth. PDT targeted to SST2 receptors was much more effective than untargeted PDT or PDT targeted to EGF receptors. The use of octreotate to target SST2 receptors expressed on tumor vessels is an excellent approach to PDT with few recurrences and some long term cures.
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影响因子：
8.8
作者：
Adams, RL;Adams, IP;Lindow, SW;Zhong, W;Atkin, SL
通讯作者：
Atkin, SL
表皮生长因子受体抑制通过血管正常化调节微环境，从而提高化疗和放疗疗效。
影响因子：
3.7
作者：
Cerniglia, George J.;Pore, Nabendu;Tsai, Jeff H.;Schultz, Susan;Mick, Rosemarie;Choe, Regine;Xing, Xiaoman;Durduran, Turgut;Yodh, Arjun G.;Evans, Sydney M.;Koch, Cameron J.;Hahn, Stephen M.;Quon, Harry;Sehgal, Chandra M.;Lee, William M. F.;Maity, Amit
通讯作者：
Maity, Amit
影响因子：
13.3
作者：
Dreaden, Erik C.;Mwakwari, Sandra C.;Austin, Lauren A.;Kieffer, Matthew J.;Oyelere, Adegboyega K.;El-Sayed, Mostafa A.
通讯作者：
El-Sayed, Mostafa A.
影响因子：
9.7
作者：
BERTRAM, JS;JANIK, P
通讯作者：
JANIK, P
影响因子：
82.9
作者：
Contrino, J;Hair, G;Rickles, FR
通讯作者：
Rickles, FR