Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2511-6. doi: 10.1073/pnas.1213657110. Epub 2013 Jan 23.
New therapies that challenge existing paradigms are needed for the treatment of cancer. We report a nanoparticle-enabled therapeutic approach to B-cell lymphoma using synthetic high density lipoprotein nanoparticles (HDL-NPs). HDL-NPs are synthesized using a gold nanoparticle template to control conjugate size and ensure a spherical shape. Like natural HDLs, biomimetic HDL-NPs target scavenger receptor type B-1, a high-affinity HDL receptor expressed by lymphoma cells. Functionally, compared with natural HDL, the gold NP template enables differential manipulation of cellular cholesterol flux in lymphoma cells, promoting cellular cholesterol efflux and limiting cholesterol delivery. This combination of scavenger receptor type B-1 binding and relative cholesterol starvation selectively induces apoptosis. HDL-NP treatment of mice bearing B-cell lymphoma xenografts selectively inhibits B-cell lymphoma growth. As such, HDL-NPs are biofunctional therapeutic agents, whose mechanism of action is enabled by the presence of a synthetic nanotemplate. HDL-NPs are active in B-cell lymphomas and potentially, other malignancies or diseases of pathologic cholesterol accumulation.
需要新的治疗方法来挑战现有的癌症治疗模式。我们报告了一种使用合成高密度脂蛋白纳米颗粒（HDL-NPs）治疗 B 细胞淋巴瘤的治疗方法。HDL-NPs 是使用金纳米颗粒模板合成的，以控制结合物的大小并确保其呈球形。与天然 HDL 一样，仿生 HDL-NPs 靶向 B 型清道夫受体 1，这是一种高亲和力的 HDL 受体，在淋巴瘤细胞中表达。在功能上，与天然 HDL 相比，金 NP 模板能够改变淋巴瘤细胞中细胞胆固醇的流动，促进细胞胆固醇外流并限制胆固醇的传递。这种清道夫受体 1 结合和相对胆固醇饥饿的组合选择性地诱导细胞凋亡。HDL-NP 治疗携带 B 细胞淋巴瘤异种移植物的小鼠选择性地抑制 B 细胞淋巴瘤的生长。因此，HDL-NPs 是具有生物功能的治疗剂，其作用机制是由于存在合成纳米模板。HDL-NPs 在 B 细胞淋巴瘤中具有活性，并且可能在其他恶性肿瘤或病理性胆固醇积累的疾病中具有活性。
