恶性黑色素瘤是一种高恶性、侵袭性强的皮肤肿瘤，全球发病率和死亡率逐年增加。由于其对化疗药物如多柔比星的敏感性差、严重副作用和药物耐药性，限制了其在黑色素瘤治疗中的有效性。最近的研究表明，免疫治疗与化疗的联合应用具有协同增强抗肿瘤效应的作用。在本研究中，我们开发了载有绿原酸（CA）和多柔比星（DOX）的脂质体，并修饰有唾液酸-八十二碳胺共轭物（SA-ODA），命名为CA-DOX-SAL，通过识别肿瘤相关巨噬细胞上的Siglec-1受体，促进药物传递。物理化学研究表明，CA-DOX-SAL的粒径和静电电位分别为128.3±0.8 nm和-4.33±0.50 mV。体外实验显示，CA-DOX-SAL通过SA受体介导的与肿瘤相关巨噬细胞的靶向作用，表现出强大的细胞摄取能力，并对肿瘤细胞产生更强的细胞毒性。体内实验发现，靶向脂质体在肿瘤区域积累，提高了抗肿瘤效果。此外，CA-DOX-SAL通过促进肿瘤促进型M2型到抗肿瘤型M1型的转变和直接杀伤肿瘤细胞，有效抑制了B16F10黑色素瘤的生长。总体而言，免疫调节剂CA和化疗药物DOX的联合递送在黑色素瘤治疗中呈现出有前景的治疗策略，可以增强临床疗效。 © 2023 Controlled Release Society.

Malignant melanoma is a high-grade aggressive skin tumor with an increasing incidence and mortality rates worldwide. Chemotherapeutic drugs such as doxorubicin have limited efficacy against melanoma due to their poor sensitivity, severe side effects, and drug resistance. Recent studies have shown that combinations of immunotherapy and chemotherapy have a synergistic effect in enhancing the anti-tumor effect. Here, we have developed liposomes co-loaded with chlorogenic acid (CA) and doxorubicin (DOX), modified with sialic acid-octadecylamine conjugate (SA-ODA), designated CA-DOX-SAL, that facilitate drug delivery by recognizing Siglec-1 receptor on TAMs. The physicochemical studies revealed the particle size and zeta potential of CA-DOX-SAL as 128.3 ± 0.8 nm and - 4.33 ± 0.50 mV, respectively. In vitro, CA-DOX-SAL demonstrated robust cellular uptake through SA receptor-mediated tumor-associated macrophages (TAM) targeting and exerted greater cytotoxicity on tumor cells. In vivo, targeted liposomes were found to accumulate in the tumor area, leading to an improvement in anti-tumor efficacy. In addition, CA-DOX-SAL effectively inhibited B16F10 melanoma tumor growth by stimulating the transition from tumor-promoting M2-type to anti-tumor M1-type and directly killing tumor cells. Overall, the co-delivery of immunomodulatory CA and chemotherapeutic DOX presents a promising therapeutic strategy to enhance clinical outcomes in the treatment of melanoma.© 2023. Controlled Release Society.