The combination of a photosensitizer and indoleamine-2,3 dioxygenase (IDO) inhibitor provides a promising photoimmunotherapy (PIT) strategy for melanoma treatment. A dual drug delivery system offers a potential approach for optimizing the inhibitory effects of PIT on melanoma proliferation and metastasis. To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis. We constructed a multifunctional nano-porphyrin material (P18-APBA-HA) using the photosensitizer-purpurin 18 (P18), hyaluronic acid (HA), and 4-(aminomethyl) phenylboronic acid (APBA). The resulting P18-APBA-HA was inserted into a phospholipid membrane and the IDO inhibitor epacadostat (EPA) was loaded into the internal phase to prepare a dual drug delivery system (Lip\EPA\P18-APBA-HA). Moreover, we also investigated its physicochemical properties, targeting, anti-tumor immunity, and anti-tumor proliferation and metastasis effects. The designed system utilized the pH sensitivity of borate ester to realize an enhanced-targeting strategy to facilitate the drug distribution in tumor lesions and efficient receptor-mediated cellular endocytosis. The intracellular release of EPA from Lip\EPA\P18-APBA-HA was triggered by thermal radiation, thereby inhibiting IDO activity in the tumor microenvironment, and promoting activation of the immune response. Intravenous administration of Lip\EPA\P18-APBA-HA effectively induced anti-tumor immunity by promoting dendritic cell maturation, cytotoxic T cell activation, and regulatory T cell suppression, and regulating cytokine secretion, to inhibit the proliferation of melanoma and lung metastasis. The proposed nano-drug delivery system holds promise as offers a promising strategy to enhance the inhibitory effects of the combination of EPA and P18 on melanoma proliferation and metastasis.

中文翻译：

---

设计靶向双药物递送系统以提高光免疫疗法对抗黑色素瘤增殖和转移的功效


光敏剂和吲哚胺-2,3双加氧酶（IDO）抑制剂的组合为黑色素瘤治疗提供了一种有前途的光免疫疗法（PIT）策略。双药物递送系统为优化 PIT 对黑色素瘤增殖和转移的抑制作用提供了一种潜在的方法。开发基于PIT的双重给药系统并研究其抑制黑色素瘤增殖和转移的功效。我们利用光敏剂红紫素18（P18）、透明质酸（HA）和4-（氨甲基）苯基硼酸（APBA）构建了多功能纳米卟啉材料（P18-APBA-HA）。将所得的P18-APBA-HA插入磷脂膜中，并将IDO抑制剂epacadostat（EPA）加载到内相中，制备双药物递送系统（Lip\EPA\P18-APBA-HA）。此外，我们还研究了其理化性质、靶向性、抗肿瘤免疫、抗肿瘤增殖和转移作用。设计的系统利用硼酸酯的pH敏感性来实现增强的靶向策略，以促进药物在肿瘤病灶中的分布和有效的受体介导的细胞内吞作用。热辐射触发Lip\EPA\P18-APBA-HA在细胞内释放EPA，从而抑制肿瘤微环境中的IDO活性，促进免疫反应的激活。静脉注射Lip\EPA\P18-APBA-HA可通过促进树突状细胞成熟、细胞毒性T细胞活化和调节性T细胞抑制，以及调节细胞因子分泌，有效诱导抗肿瘤免疫，从而抑制黑色素瘤的增殖和肺转移。 所提出的纳米药物递送系统有望提供一种有前景的策略来增强 EPA 和 P18 组合对黑色素瘤增殖和转移的抑制作用。