A Nanoparticle Carrier for Co-Delivery of Gemcitabine and Small Interfering RNA in Pancreatic Cancer Therapy
A Nanoparticle Carrier for Co-Delivery of Gemcitabine and Small Interfering RNA in Pancreatic Cancer Therapy
复制标题
用于在胰腺癌治疗中共同递送吉西他滨和小干扰 RNA 的纳米颗粒载体
DOI：
10.1166/jbn.2016.2269
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发表时间：
2016-08-01
影响因子：
2.9
通讯作者：
Huang, Kaihong
中科院分区：
文献类型：
--
作者：
Li, Jiajia;Chen, Yinting;Huang, Kaihong
背景：精准医疗的概念在治疗癌症方面显示出前景，化疗药物和靶基因的共同递送载体是基础研究和临床应用的关键工具。为了解决这个问题，我们开发了一种癌症靶向纳米颗粒载体，将吉西他滨 (Gem) 和小干扰 RNA (siRNA) 转移至胰腺癌。方法：在 15 nm 处共振的氧化铁纳米粒子 (IONP) 与针对 CD44v6 的单链可变片段 (scFv) (scFv(CD44v6)) 缀合，正如我们之前的研究所报道的，这已证明其具有胰腺癌靶向特异性。然后通过溶酶体可裂解的四肽接头连接 Gem，形成 SCFv 靶向纳米颗粒构建体，随后将其与靶向 Bmi-1 癌基因 (siBmi-1) 的 siRNA 缀合，以获得多功能纳米颗粒 scFv-Gem-siBmi-1-NPs。进行了一系列生物学实验来测试其生物物理特性、基因沉默功效以及体外和体内抗肿瘤作用。结果：该多功能纳米粒子不仅具有约80 nm的超小尺寸、优异的生物相容性和生物降解性，而且在体外和体内发挥协同抗肿瘤作用，如抑制肿瘤细胞生长、侵袭和迁移，减缓细胞周期进程，促进肿瘤细胞凋亡。此外，这种纳米颗粒可以在体内有效地靶向胰腺癌，从而增强 Gem 的生物利用度和功效。结论：scFv-Gem-siBmi-1-NPs可有效、靶向地将Gem和siBmi-1共同递送至胰腺癌，并发挥高效、协同的抗肿瘤治疗作用。这种前瞻性载体显示出精确治疗胰腺癌的希望。
Background: The concept of precision medicine to treat cancer shows promise and a co-delivery carrier for chemotherapy drugs and target genes is the key tool for both basic research and clinical application. To address this, we developed a cancer-targeting nanoparticle vector to transfer gemcitabine (Gem) and small interfering RNA (siRNA) to pancreatic cancer. Methods: Iron oxide nanoparticles (IONPs) resonant at 15 nm were conjugated with the single chain variable fragment (scFv) against CD44v6 (scFv(CD44v6)), which has proven pancreatic cancer-targeting specificity as reported in our previous study. Gem was then linked through a lysosomally cleavable tetrapeptide linker, resulting in a scFv-targeted nanoparticle construct, which was subsequently conjugated to siRNA targeting the Bmi-1 oncogene (siBmi-1) to obtain the multifunctional nanoparticle scFv-Gem-siBmi-1-NPs. A series of biological experiments were performed to test its biophysical characterization, gene silencing efficacy and anti-tumor effect in vitro and in vivo. Results: The multifunctional nanoparticle not only possesses an ultra-small size of approximately 80 nm, excellent biocompatibility and biodegradability, but also exerts a synergistic anti-tumor effect both in vitro and in vivo, such as inhibition of tumor cell growth, invasion and migration, reduction of cell cycle progression and promotion of tumor apoptosis. Furthermore, this nanoparticle can efficiently target pancreatic cancer in vivo, resulting in the enhanced bioavailability and efficacy of Gem. Conclusion: scFv-Gem-siBmi-1-NPs provide an effective and targeted co-delivery of Gem and siBmi-1 to pancreatic cancer, and exert an efficient and corporate anti-tumor therapeutic effect. This prospective vector shows promise for precise treatment of pancreatic cancer.