Bio-Organic Chemistry, Department of Chemical Engineering and Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology Helix, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Laboratory of Immunoengineering, Department of Biomedical Engineering, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Biomacromolecules. 2024 May 13;25(5):3044-3054. doi: 10.1021/acs.biomac.4c00141. Epub 2024 Apr 25.
Photodynamic therapy (PDT) has demonstrated efficacy in eliminating local tumors, yet its effectiveness against metastasis is constrained. While immunotherapy has exhibited promise in a clinical context, its capacity to elicit significant systemic antitumor responses across diverse cancers is often limited by the insufficient activation of the host immune system. Consequently, the combination of PDT and immunotherapy has garnered considerable attention. In this study, we developed pH-responsive porphyrin-peptide nanosheets with tumor-targeting capabilities (PRGD) that were loaded with the IDO inhibitor NLG919 for a dual application involving PDT and immunotherapy (PRGD/NLG919). In vitro experiments revealed the heightened cellular uptake of PRGD/NLG919 nanosheets in tumor cells overexpressing αvβ3 integrins. The pH-responsive PRGD/NLG919 nanosheets demonstrated remarkable singlet oxygen generation and photocytotoxicity in HeLa cells in an acidic tumor microenvironment. When treating HeLa cells with PRGD/NLG919 nanosheets followed by laser irradiation, a more robust adaptive immune response occurred, leading to a substantial proliferation of CD3CD8 T cells and CD3CD4 T cells compared to control groups. Our pH-responsive targeted PRGD/NLG919 nanosheets therefore represent a promising nanosystem for combination therapy, offering effective PDT and an enhanced host immune response.
光动力疗法 (PDT) 在消除局部肿瘤方面已被证明具有疗效，但在治疗转移瘤方面的效果受到限制。免疫疗法在临床环境中已显示出一定的疗效，但由于宿主免疫系统的激活不足，其在多种癌症中引发显著全身抗肿瘤反应的能力往往受到限制。因此，PDT 和免疫疗法的联合应用引起了广泛关注。在本研究中，我们开发了具有肿瘤靶向能力的 pH 响应卟啉-肽纳米片 (PRGD)，并负载 IDO 抑制剂 NLG919，用于 PDT 和免疫疗法的双重应用（PRGD/NLG919）。体外实验表明，在过度表达 αvβ3 整合素的肿瘤细胞中，PRGD/NLG919 纳米片的细胞摄取率更高。在酸性肿瘤微环境中，pH 响应的 PRGD/NLG919 纳米片在 HeLa 细胞中表现出显著的单线态氧生成和光细胞毒性。当用 PRGD/NLG919 纳米片处理 HeLa 细胞并随后进行激光照射时，与对照组相比，适应性免疫反应更强烈，导致 CD3CD8 T 细胞和 CD3CD4 T 细胞大量增殖。因此，我们的 pH 响应靶向 PRGD/NLG919 纳米片代表了一种有前途的联合治疗纳米系统，提供有效的 PDT 和增强的宿主免疫反应。
