Abstract：
BACKGROUND: 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.
OBJECTIVE: To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：光敏剂和吲哚胺-2,3双加氧酶（IDO）抑制剂的组合为黑素瘤治疗提供了有前途的光免疫疗法（PIT）策略。双重药物递送系统为优化PIT对黑素瘤增殖和转移的抑制作用提供了潜在的方法。
目的：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。
方法：我们使用光敏剂-紫癜18（P18）构建了多功能纳米卟啉材料（P18-APBA-HA），透明质酸（HA），和4-(氨基甲基)苯基硼酸(APBA)。将所得的P18-APBA-HA插入磷脂膜，并将IDO抑制剂epacadostat（EPA）加载到内相中，以制备双重药物递送系统（Lip\\EPA\\P18-APBA-HA）。此外，我们还研究了它的物理化学性质，瞄准,抗肿瘤免疫，以及抗肿瘤增殖和转移的作用。
结果：设计的系统利用硼酸酯的pH敏感性来实现增强靶向策略，以促进药物在肿瘤病变中的分布和有效的受体介导的细胞内吞作用。从Lip\\EPA\\P18-APBA-HA的细胞内释放EPA是由热辐射触发的，从而抑制肿瘤微环境中的IDO活性，并促进免疫反应的激活。静脉给药Lip\\EPA\\P18-APBA-HA通过促进树突状细胞成熟有效诱导抗肿瘤免疫,细胞毒性T细胞活化，和调节性T细胞抑制，调节细胞因子分泌，抑制黑色素瘤的增殖和肺转移。
结论：所提出的纳米药物递送系统有望为增强EPA和P18组合对黑色素瘤增殖和转移的抑制作用提供有希望的策略。
目的：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。
方法：我们使用光敏剂-紫癜18（P18）构建了多功能纳米卟啉材料（P18-APBA-HA），透明质酸（HA），和4-(氨基甲基)苯基硼酸(APBA)。将所得的P18-APBA-HA插入磷脂膜，并将IDO抑制剂epacadostat（EPA）加载到内相中，以制备双重药物递送系统（Lip\\EPA\\P18-APBA-HA）。此外，我们还研究了它的物理化学性质，瞄准,抗肿瘤免疫，以及抗肿瘤增殖和转移的作用。
结果：设计的系统利用硼酸酯的pH敏感性来实现增强靶向策略，以促进药物在肿瘤病变中的分布和有效的受体介导的细胞内吞作用。从Lip\\EPA\\P18-APBA-HA的细胞内释放EPA是由热辐射触发的，从而抑制肿瘤微环境中的IDO活性，并促进免疫反应的激活。静脉给药Lip\\EPA\\P18-APBA-HA通过促进树突状细胞成熟有效诱导抗肿瘤免疫,细胞毒性T细胞活化，和调节性T细胞抑制，调节细胞因子分泌，抑制黑色素瘤的增殖和肺转移。
结论：所提出的纳米药物递送系统有望为增强EPA和P18组合对黑色素瘤增殖和转移的抑制作用提供有希望的策略。
