In vitro targeted photodynamic therapy with a pyropheophorbide--a conjugated inhibitor of prostate-specific membrane antigen.
In vitro targeted photodynamic therapy with a pyropheophorbide--a conjugated inhibitor of prostate-specific membrane antigen.
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DOI：
10.1002/pros.20909
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发表时间：
2009-05-01
期刊：
影响因子：
2.8
通讯作者：
Berkman, Clifford E.
中科院分区：
文献类型：
--
作者：
Liu, Tiancheng;Wu, Lisa Y.;Choi, Joseph K.;Berkman, Clifford E.
光敏剂（PS）的特异性递送的缺乏代表了癌症的光动力疗法（PDT）的显著限制。生物标志物前列腺特异性膜抗原（PSMA）作为前列腺癌的成像和治疗应用的靶标已经引起了相当大的关注。尽管最近已经努力将PSMA的抑制剂与成像剂缀合，但是还没有关于光敏剂缀合的PSMA抑制剂用于前列腺癌的靶向PDT的报道。本研究集中于焦脱镁叶绿酸-a的PSMA受体-缀合物（Ppa-缀合物2）用于靶向PDT以实现PSMA+ LNCaP细胞中的凋亡的用途。共聚焦激光扫描显微镜与核染色和免疫荧光方法相结合，用于监测特异性成像和PDT介导的对PSMA阳性LNCaP和PSMA阴性（PC-3）细胞的凋亡作用。我们的结果表明，Ppa-共轭物2的PDT介导的作用是特异性的LNCaP细胞，但不是PC-3细胞。通过HOE 33342/PI双染色，早在2 h就检测到细胞通透性，4 h时变得更强。细胞凋亡半胱天冬酶级联被激活的证据是基于PARP p85片段的出现。PDT后16 h TUNEL法检测到DNA片段化，证实了凋亡事件。HOE 33342/PI双染色的细胞渗透性以及PARP p85片段和TUNEL试验证实了PS抑制剂结合物2处理并随后辐照时PSMA+细胞中的细胞凋亡。预期该缀合物的PSMA靶向小分子可以用作PDT和前列腺癌的其他治疗应用的递送载体。
The lack of specific delivery of photosensitizers (PSs), represents a significant limitation of photodynamic therapy (PDT) of cancer. The biomarker prostate-specific membrane antigen (PSMA) has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. Although recent efforts have been made to conjugate inhibitors of PSMA with imaging agents, there have been no reports on photosensitizer-conjugated PSMA inhibitors for targeted PDT of prostate cancer. The present study focuses on the use of a PSMA inhibitor-conjugate of pyropheophorbide-a (Ppa-conjugate 2) for targeted PDT to achieve apoptosis in PSMA+ LNCaP cells. Confocal laser scanning microscopy with a combination of nuclear staining and immunofluorescence methods were employed to monitor the specific imaging and PDT-mediated apoptotic effects on PSMA-positive LNCaP and PSMA-negative (PC-3) cells. Our results demonstrated that PDT-mediated effects by Ppa-conjugate 2 were specific to LNCaP cells, but not PC-3 cells. Cell permeability was detected as early as 2 h by HOE33342/PI double-staining, becoming more intense by 4 h. Evidence for the apoptotic caspase cascade being activated was based on the appearance of PARP p85 fragment. TUNEL assay detected DNA fragmentation 16 h post-PDT, confirming apoptotic events. Cell permeability by HOE33342/PI double-staining as well as PARP p85 fragment and TUNEL assays confirm cellular apoptosis in PSMA+ cells when treated with PS-inhibitor conjugate 2 and subsequently irradiated. It is expected that the PSMA targeting small-molecule of this conjugate can serve as a delivery vehicle for PDT and other therapeutic applications for prostate cancer.
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影响因子：
5.6
作者：
Hsieh, YJ;Wu, CC;Yu, JS
通讯作者：
Yu, JS
DOI：
10.1016/s1056-8719(97)00033-6
发表时间：
1997-06-01
影响因子：
1.9
作者：
Allen, RT;Hunter, WJ;Agrawal, DK
通讯作者：
Agrawal, DK
影响因子：
3.5
作者：
Anderson, Marc O.;Wu, Lisa Y.;Berkman, Clifford E.
通讯作者：
Berkman, Clifford E.
影响因子：
64.8
作者：
Enari, M;Sakahira, H;Nagata, S
通讯作者：
Nagata, S
影响因子：
3.3
作者：
Allison, Ron R.;Downie, Gordon H.;Sibata, Claudio H.
通讯作者：
Sibata, Claudio H.