Li Jiajia, Chen Yinting, Zeng Linjuan, Lian Guoda, Chen Shaojie, Li Yaqing, Yang Kege, Huang Kaihong
J Biomed Nanotechnol. 2016 Aug;12(8):1654-66. doi: 10.1166/jbn.2016.2269.
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 (scFvCD44v6), 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.
精准医学治疗癌症的概念显示出前景，化疗药物和靶基因的共递送载体是基础研究和临床应用的关键工具。为解决这一问题，我们开发了一种癌症靶向纳米颗粒载体，用于将吉西他滨（Gem）和小干扰RNA（siRNA）递送至胰腺癌。
将在15 nm处共振的氧化铁纳米颗粒（IONPs）与针对CD44v6的单链可变片段（scFv）（scFvCD44v6）偶联，如我们先前研究报道，其已被证实具有胰腺癌靶向特异性。然后通过可被溶酶体裂解的四肽接头连接Gem，得到scFv靶向纳米颗粒构建体，随后将其与靶向Bmi-1癌基因的siRNA（siBmi-1）偶联，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，以测试其在体外和体内的生物物理特性、基因沉默效果和抗肿瘤作用。
该多功能纳米颗粒不仅具有约80 nm的超小尺寸、优异的生物相容性和生物降解性，而且在体外和体内均发挥协同抗肿瘤作用，如抑制肿瘤细胞生长、侵袭和迁移、减少细胞周期进程以及促进肿瘤细胞凋亡。此外，这种纳米颗粒能够在体内有效靶向胰腺癌，从而提高Gem的生物利用度和疗效。
scFv-Gem-siBmi-1-NPs为胰腺癌提供了Gem和siBmi-1的有效靶向共递送，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准治疗胰腺癌的前景。
