Mukherjee Priyabrata, Bhattacharya Resham, Bone Nancy, Lee Yean K, Patra Chitta Ranjan, Wang Shanfeng, Lu Lichun, Secreto Charla, Banerjee Pataki C, Yaszemski Michael J, Kay Neil E, Mukhopadhyay Debabrata
Department of Biochemistry and Molecular Biology, 200 1st Street, Mayo Clinic Rochester, MN 55905, USA.
J Nanobiotechnology. 2007 May 8;5:4. doi: 10.1186/1477-3155-5-4.
B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL.
B 细胞慢性淋巴细胞白血病（CLL）是一种无法治愈的疾病，主要特征为抗凋亡。我们之前描述过一种在 CLL B 细胞中产生抗凋亡作用的 VEGF 信号通路。我们发现，与抗 VEGF 抗体共培养可使 CLL B 细胞诱导出明显更多的凋亡。为提高这些药物在 CLL 治疗中的疗效，我们专注于金纳米颗粒（GNP）的应用。选择金纳米颗粒是基于其生物相容性、非常高的表面积、易于表征和表面功能化。我们将 VEGF 抗体（AbVF）附着于金纳米颗粒上，并测定其杀死 CLL B 细胞的能力。使用紫外可见光谱（UV-Vis）、透射电子显微镜（TEM）、热重分析（TGA）和 X 射线光电子能谱（XPS）对金纳米颗粒及其纳米缀合物进行表征。所有研究的患者样本（N = 7）对金-AbVF 治疗均有反应，CLL B 细胞呈剂量依赖性凋亡。金-AbVF 诱导的凋亡明显高于仅暴露于 AbVF 或 GNP 的 CLL 细胞。经金-AbVF 处理的细胞显示抗凋亡蛋白显著下调，并出现 PARP 裂解。经金-AbVF 处理和 GNP 处理的细胞在早期和晚期内体以及多囊泡体中显示纳米颗粒的内化。单独的未包被金纳米颗粒能够在 CLL B 细胞中诱导一定程度的凋亡。本文为使用金纳米颗粒治疗 CLL-B 开辟了新机会，并将纳米科学与 CLL 治疗相结合。未来，利用金纳米颗粒的光电特性治疗 CLL 存在潜在机会。
