新型免疫靶向纳米粒介导免疫治疗与光动力治疗在乳腺癌中的应用

Immune targeted therapy has been committed to concentrating drugs at tumor sites on an oriented basis to motivate and enhance body immunity so as to eliminate tumor cells. Studies have discovered that expression of CD47 in breast cancer tissue was several times higher than that in the normal tissue and was positively correlated with tumor malignancy. In this study, the PEGylated PAMAM is loaded with photosensitizer IR820 and catalase (CAT), and CD47mAb is linked on its surface to synthesize immune targeted nanoparticle, CD47mAb-PAMAM-IR820-CAT. When entering tumor sites, CD47mAb on the surface of nanoparticles can bind to CD47 to block CD47/SIRPa interaction, thereby activating immunocompetence of macrophages and further mediating nanoparticle uptake. In addition, CAT in nanoparticles can catalyze H2O2 to produce O2, thereby alleviating local hypoxia, increasing PDT effectiveness and inducing tumor-associated macrophages to transform from M2 type to M1 type. Dead tumor cells will release antigens, proteases, reactive oxygen and cytokines to further chemotactic and activate macrophages. This study combines macrophage-based immunotherapy with PDT with a view to improving therapy targeting and safety, hoping to provide new strategies for breast cancer treatment.

免疫靶向治疗致力于将药物定向浓集至肿瘤，激发和增强机体免疫功能，以消灭肿瘤细胞。研究发现CD47在乳腺癌组织中的表达量是正常组织数倍，且与肿瘤的恶性程度呈正相关。本研究拟以PEG化PAMAM为载体，装载光敏剂IR820和过氧化氢酶CAT，并在其表面链接CD47mAb，合成具有免疫靶向能力的纳米粒CD47mAb-PAMAM-IR820-CAT。纳米粒进入肿瘤局部，其表面的 CD47mAb与CD47结合阻断CD47/SIRPa作用，进而活化巨噬细胞免疫活性，进一步介导纳米粒入胞。此外，进入肿瘤部位的纳米粒中的CAT能够催化H2O2产生O2，改善局部低氧状态，提高PDT作用，并诱导肿瘤相关巨噬细胞由M2型向M1型转化。死亡的肿瘤细胞释放抗原、蛋白酶、活性氧和细胞因子，进一步趋化和活化巨噬细胞。本研究从治疗靶向性和安全性入手，将基于巨噬细胞的免疫治疗和PDT结合起来，希望为乳腺癌治疗提供新的策略。

免疫靶向治疗致力于将药物定向浓集至肿瘤，激发和增强机体免疫功能，以消灭肿瘤细胞。研究发现CD47在乳腺癌组织中的表达量是正常组织数倍，且与肿瘤的恶性程度呈正相关。本研究以PEG化PAMAM为载体，装载光敏剂IR820和过氧化氢酶CAT，并在其表面链接CD47mAb，合成具有免疫靶向能力的纳米粒CD47mAb-PAMAM-IR820-CAT。纳米粒进入肿瘤局部，其表面的CD47mAb与CD47结合阻断CD47/SIRPa作用，进而活化巨噬细胞免疫活性，进一步介导纳米粒入胞。此外，进入肿瘤部位的纳米粒中的CAT能够催化H2O2产生O2，改善局部低氧状态，提高PDT作用，并诱导肿瘤相关巨噬细胞由M2型向M1型转化。死亡的肿瘤细胞释放抗原、蛋白酶、活性氧和细胞因子，进一步趋化和活化巨噬细胞。本研究从治疗靶向性和安全性入手，将基于巨噬细胞的免疫治疗和PDT结合起来，为乳腺癌治疗提供新的策略。