Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis.
Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis.
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金纳米颗粒在B-气淋巴细胞性白血病（BCLL）中的潜在治疗应用：增强细胞凋亡。
DOI：
10.1186/1477-3155-5-4
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发表时间：
2007-05-08
影响因子：
10.2
通讯作者：
Mukhopadhyay, Debabrata
中科院分区：
文献类型：
--
作者：
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
B慢性淋巴细胞白血病（CLL）是一种主要以细胞凋亡抵抗为特征的不治之症。我们之前描述了在 CLL B 细胞中产生凋亡抵抗的 VEGF 信号通路。我们发现通过与抗 VEGF 抗体共培养，可以诱导 CLL B 细胞明显更多的凋亡。为了提高这些药物在 CLL 治疗中的功效，我们重点关注金纳米颗粒 (GNP) 的使用。选择金纳米粒子是基于其生物相容性、极高的表面积、易于表征和表面功能化。我们将 VEGF 抗体 (AbVF) 连接到金纳米粒子上，并确定其杀死 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) 对金纳米粒子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 细胞出现剂量依赖性凋亡。金-AbVF 诱导的细胞凋亡显着高于仅暴露于 AbVF 或 GNP 的 CLL 细胞。金-AbVF 处理的细胞表现出抗凋亡蛋白的显着下调，并表现出 PARP 裂解。金-AbVF 处理和 GNP 处理的细胞显示纳米颗粒在早期和晚期内体以及多泡体中的内化。单独未包被的金纳米粒子能够诱导 CLL B 细胞一定程度的细胞凋亡。本文为使用金纳米粒子治疗 CLL-B 开辟了新的机会，并将纳米科学与 CLL 治疗相结合。未来，存在利用金纳米粒子的光电特性治疗慢性淋巴细胞白血病的潜在机会。
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.
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DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
影响因子：
3.4
作者：
Koide, T;Kojima, T;Kamei, H
通讯作者：
Kamei, H
影响因子：
10.8
作者：
El-Sayed, IH;Huang, XH;El-Sayed, MA
通讯作者：
El-Sayed, MA
影响因子：
4.7
作者：
Goodman, CM;McCusker, CD;Rotello, VM
通讯作者：
Rotello, VM
影响因子：
3.3
作者：
Bourg, MC;Badia, A;Lennox, RB
通讯作者：
Lennox, RB