Korea Institute of Radiological & Medical Sciences , Nowonro 75, Nowon-gu, Seoul 01812 , Republic of Korea.
ACS Appl Mater Interfaces. 2018 Nov 28;10(47):40424-40433. doi: 10.1021/acsami.8b14968. Epub 2018 Nov 14.
Heme oxygenase-1 (HO-1) is a stress-response protein with potent cytoprotective and antioxidant activity, and its expression in cancer cells is enhanced in response to chemotherapy and radiotherapy. HO-1 is known to serve as a shield to protect cancer cells from anticancer therapy and attenuate apoptotic signals. It can be therefore reasoned that inhibition of HO-1 reduces the antioxidant level, making cancer cells more sensitive to photothermal heating. In this work, we developed dual imaging-guided oxidative-photothermal combination nanotherapeutics (OPCN) consisting of amphiphilic polymers conjugated with zinc protoporphyrin as a HO-1 inhibitor and fluorescent IR820 as a photothermal agent. A combination of OPCN and near-infrared (NIR) laser irradiation markedly increased the temperature and exerted significant toxicity through induction of apoptosis. In a mouse model of xenografts, tumors were identified by the strong fluorescence and photoacoustic signals. OPCN combined with NIR laser irradiation resulted in effective and complete thermal ablation of tumors without discernable side effects and tumor recurrence. We believe that OPCN hold tremendous translational potential for dual imaging-guided oxidative-photothermal combination anticancer therapy.
血红素加氧酶-1（HO-1）是一种应激反应蛋白，具有强大的细胞保护和抗氧化活性，其在癌细胞中的表达在化疗和放疗中增强。HO-1 被认为是一种保护癌症细胞免受抗癌治疗和减轻凋亡信号的盾牌。因此，可以推断抑制 HO-1 会降低抗氧化水平，使癌细胞对光热加热更敏感。在这项工作中，我们开发了由两亲聚合物与锌原卟啉作为 HO-1 抑制剂和荧光 IR820 作为光热剂缀合而成的双重成像引导氧化-光热联合纳米治疗剂（OPCN）。OPCN 与近红外（NIR）激光照射的组合显着提高了温度，并通过诱导细胞凋亡产生了显著的毒性。在异种移植小鼠模型中，肿瘤通过强烈的荧光和光声信号进行识别。OPCN 与 NIR 激光照射相结合导致肿瘤的有效和完全热消融，而无明显的副作用和肿瘤复发。我们相信，OPCN 为双重成像引导的氧化-光热联合抗癌治疗提供了巨大的转化潜力。
