Tropomyosin Receptor Kinase C Targeted Delivery of a Peptidomimetic Ligand-Photosensitizer Conjugate Induces Antitumor Immune Responses Following Photodynamic Therapy.
Tropomyosin Receptor Kinase C Targeted Delivery of a Peptidomimetic Ligand-Photosensitizer Conjugate Induces Antitumor Immune Responses Following Photodynamic Therapy.
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DOI：
10.1038/srep37209
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发表时间：
2016-11-17
影响因子：
4.6
通讯作者：
Lee HB
中科院分区：
文献类型：
--
作者：
Kue CS;Kamkaew A;Voon SH;Kiew LV;Chung LY;Burgess K;Lee HB
制备了靶向原肌球蛋白受体激酶C（TrkC）的配体-光敏剂构建体IYIY-二碘-硼-二吡咯亚甲基（IYIY-I2-BODIPY）及其乱序对应物IYII-I2-BODIPY。IYIY-I2-B 0 DIPY与神经营养因子-3（NT-3）类似地结合TrkC，并且已报道NT-3调节免疫应答。此外，它可以表明，光动力疗法（PDT）提高抗肿瘤免疫反应。这促使我们研究IYIY-I2-BODIPY在PDT前和PDT后条件下介导的免疫影响。我们证明，10 mg/kg的IYIY-I2-BODIPY（强反应）和IYI-I2-BODIPY（弱反应），而不是I2-BODIPY对照，增加了IL-2，IL-4，IL-6和IL-17的水平，但降低了全身免疫调节介质TGF-β，骨髓源性抑制细胞和调节性T细胞的水平。只有IYIY-I2-BODIPY增强了IFN-γ+和IL-17+ T淋巴细胞，并在每天给药5天时延迟了小鼠中的肿瘤生长（尺寸减小约20%）。所有这些效应均在无辐照的情况下观察到;当辐照（520 nm，100 J/cm 2，160 mW/cm 2）以产生PDT效应（药物-光间隔1 h）时，IYIY-I2-BODIPY诱导更强的反应。此外，与对照相比，光照射的IYIY-I2-BODIPY处理的小鼠具有高水平的效应T细胞。从IYIY-I2-BODIPY处理的经光照射的存活小鼠连续转移免疫细胞在受体小鼠中显著延迟了肿瘤生长（尺寸小约40-50%）。IYIY-I2-BODIPY单独和与PDT组合以抑制肿瘤生长的方式调节免疫应答。与免疫抑制性常规化疗不同，IYIY-I2-BODIPY可作为免疫刺激性化疗剂，在临床癌症治疗中具有潜在应用。
Tropomyosin receptor kinase C (TrkC) targeted ligand-photosensitizer construct, IYIY-diiodo-boron-dipyrromethene (IYIY-I2-BODIPY) and its scrambled counterpart YIYI-I2-BODIPY have been prepared. IYIY-I2-BODIPY binds TrkC similar to neurotrophin-3 (NT-3), and NT-3 has been reported to modulate immune responses. Moreover, it could be shown that photodynamic therapy (PDT) elevates antitumor immune responses. This prompted us to investigate the immunological impacts mediated by IYIY-I2-BODIPY in pre- and post-PDT conditions. We demonstrated that IYIY-I2-BODIPY (strong response) and YIYI-I2-BODIPY (weak response) at 10 mg/kg, but not I2-BODIPY control, increased the levels of IL-2, IL-4, IL-6 and IL-17, but decreased the levels of systemic immunoregulatory mediators TGF-β, myeloid-derived suppressor cells and regulatory T-cells. Only IYIY-I2-BODIPY enhanced the IFN-γ+ and IL-17+ T-lymphocytes, and delayed tumor growth (~20% smaller size) in mice when administrated daily for 5 days. All those effects were observed without irradiation; when irradiated (520 nm, 100 J/cm2, 160 mW/cm2) to produce PDT effects (drug-light interval 1 h), IYIY-I2-BODIPY induced stronger responses. Moreover, photoirradiated IYIY-I2-BODIPY treated mice had high levels of effector T-cells compared to controls. Adoptive transfer of immune cells from IYIY-I2-BODIPY-treated survivor mice that were photoirradiated gave significantly delayed tumor growth (~40–50% smaller size) in recipient mice. IYIY-I2-BODIPY alone and in combination with PDT modulates the immune response in such a way that tumor growth is suppressed. Unlike immunosuppressive conventional chemotherapy, IYIY-I2-BODIPY can act as an immune-stimulatory chemotherapeutic agent with potential applications in clinical cancer treatment.
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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：
8
作者：
Jin, W.;Yun, C.;Kim, S-J
通讯作者：
Kim, S-J
影响因子：
3.9
作者：
Brodeur, GM;Nakagawara, A;Evans, AE
通讯作者：
Evans, AE
影响因子：
4
作者：
Chen, Dianjun;Brahimi, Fouad;Burgess, Kevin
通讯作者：
Burgess, Kevin
影响因子：
7.3
作者：
Kamkaew A;Burgess K
通讯作者：
Burgess K