Drug Delivery Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, United States.
Department of Radiation Oncology, Emory University School of Medicine, 1365 Clifton Road Northeast, Atlanta, GA 30322, United States.
Photodiagnosis Photodyn Ther. 2014 Jun;11(2):193-203. doi: 10.1016/j.pdpdt.2014.02.001. Epub 2014 Mar 19.
The goal of the current research is to evaluate the potential of photodynamic therapy (PDT) in the treatment of triple negative breast cancer (TNBC) with the development of a theranostic thermosensitive liposome platform to deliver indocyanine green (ICG) as the near-infrared (NIR) photosensitizer excited by an 808 nm diode laser.
In the PDT protocol, an optimized thermosensitive liposome formulation is investigated to formulate ICG as the photosensitizer, which is exited by laser light at the wavelength of 808 nm delivered by a fiber-coupled laser system. ICG in both free solution and thermosensitive liposomal formulation were evaluated as the NIR photosensitizer and compared in the PDT treatment on a panel of triple negative breast cancer cell lines along with the nontumorigenic mammary epithelial cell line MCF-10A. In addition to cytotoxicity, and clonogenic survival assessment, the role of DNA double strand break damage was evaluated.
Both MTT and clonogenic assays revealed that PDT using ICG inhibited the growth of several TNBC cell lines as well as the non-tumorigenic human breast epithelial cell line MCF-10A; and the liposomal formulation of ICG did not compromise the in vitro treatment potency, though free ICG performed slightly more effective in certain cell lines, but was not statistically significant. Cell viability was dose dependent in regards to ICG concentration and irradiation energy. Interestingly, PDT using the described protocol was more potent to inhibit the growth of MDA-MB-468 and HCC-1806 cells, coinciding with the observation that these cells are more sensitive toward DNA damaging agents. In comparison, cell lines HCC-70, BT-549, and MCF-10A were found to have less of an inhibitory effect. Furthermore, substantial DNA double strand breaks (DSBs) were observed 30 min after the PDT treatment via a γ-H2AX staining assay. PDT induced DNA damage has the potential to lead to mutagenicity, which may have various responses depending on the repair capabilities of the cells.
Our results suggest that PDT using indocyanine green loaded liposomes were effective in inhibiting tumor cell growth to varying extents with higher responses observed for MDA-MB-468 and HCC-1806 cells.
本研究的目的是开发一种治疗性热敏感脂质体平台，以递送吲哚菁绿（ICG）作为近红外（NIR）光敏剂，用 808nm 二极管激光激发，从而评估光动力疗法（PDT）在治疗三阴性乳腺癌（TNBC）中的潜力。
在 PDT 方案中，研究了一种优化的热敏感脂质体配方，将 ICG 配方为光敏剂，用光纤耦合激光系统输送的 808nm 激光激发。游离溶液和热敏脂质体配方中的 ICG 均被评估为 NIR 光敏剂，并在一系列三阴性乳腺癌细胞系以及非致瘤性乳腺上皮细胞系 MCF-10A 上进行 PDT 治疗比较。除了细胞毒性和集落存活评估外，还评估了 DNA 双链断裂损伤的作用。
MTT 和集落形成实验均表明，ICG 的 PDT 抑制了几种 TNBC 细胞系以及非致瘤性人乳腺上皮细胞系 MCF-10A 的生长；并且 ICG 的脂质体配方并没有降低体外治疗效果，尽管游离 ICG 在某些细胞系中效果稍好，但没有统计学意义。细胞活力与 ICG 浓度和辐射能量呈剂量依赖性。有趣的是，用所述方案进行 PDT 对抑制 MDA-MB-468 和 HCC-1806 细胞的生长更为有效，这与这些细胞对 DNA 损伤剂更敏感的观察结果一致。相比之下，细胞系 HCC-70、BT-549 和 MCF-10A 的抑制作用较小。此外，通过γ-H2AX 染色测定法，在 PDT 治疗后 30 分钟观察到大量 DNA 双链断裂（DSB）。PDT 诱导的 DNA 损伤有可能导致突变，这可能因细胞的修复能力而有不同的反应。
我们的结果表明，用载有吲哚菁绿的脂质体进行 PDT 在不同程度上有效抑制肿瘤细胞生长，MDA-MB-468 和 HCC-1806 细胞的反应更高。
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