Molecular Imaging Program, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA.
Cancer Sci. 2019 Dec;110(12):3689-3694. doi: 10.1111/cas.14203. Epub 2019 Oct 22.
Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon-phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR-PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample's NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR-PIT nevertheless is capable of effectively treating cancers within bone.
近红外光免疫治疗(NIR-PIT)是一种基于注射硅酞菁衍生物 IRdye 700DX(IR700)与针对癌细胞表面表达抗原的单克隆抗体的偶联物的分子靶向癌症光疗。随后局部暴露于近红外光会导致靶向癌细胞的快速和高度选择性免疫原性细胞死亡。由于许多癌症通过光无法很好穿透的骨骼生长,因此本研究的目的是确定 NIR-PIT 是否可以有效治疗骨骼中的癌症。牛肋骨被用作骨样本。由于初步测试表明该样本的近红外光透过率约为 4.52%,因此假设 128 和 1500 J/cm 的最大辐射剂量足以分别诱导体外靶细胞和体内小鼠肿瘤模型中的细胞死亡。通过比较相对荧光素酶活性和细胞毒性测定来测量细胞活力。在体外模型中,通过骨照射 NIR 光后,肿瘤细胞活力在 64 和 128 J/cm 时显著降低。体内小鼠肿瘤模型还表明,与对照组相比,通过骨照射 1500 J/cm 的 NIR 光在治疗后 24 和 48 小时均显著降低了肿瘤活力(分别为 P=0.026 和 P=0.040)。因此,尽管光传输存在限制,但 NIR-PIT 仍然能够有效地治疗骨骼内的癌症。
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