Serum-resistant complex nanoparticles functionalized with imidazole-rich polypeptide for gene delivery to pulmonary metastatic melanoma.
Serum-resistant complex nanoparticles functionalized with imidazole-rich polypeptide for gene delivery to pulmonary metastatic melanoma.
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DOI：
10.1016/j.ijpharm.2013.12.029
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发表时间：
2014-01
影响因子：
5.8
通讯作者：
Jijin Gu;Xinyi Chen;Hongliang Xin;Xiaoling Fang;X. Sha
中科院分区：
文献类型：
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作者：
Jijin Gu;Xinyi Chen;Hongliang Xin;Xiaoling Fang;X. Sha
提高血清耐药性和克服溶酶体屏障是提高非病毒基因传递系统转染效率的有效可行策略。为了实现治疗性基因的全身递送，我们先前开发了基于静电涂层的自组装羧甲基聚l-组氨酸(CM-PLH)/聚β-氨基酯(PbAE)/pDNA三元复合物纳米颗粒，作为一种有效的pDNA载体。用CM-PLH对带正电荷的pbaa /pDNA复合物进行再充电是一种降低细胞毒性和提高其体内稳定性的有前途的方法。在本研究中，进一步评价了三元复合纳米颗粒在体外和体内的转染活性。三种复合物纳米颗粒的转染效率表现出显著的血清抗性(50% FBS中含cm - plh(51.9±4.35)%，50% FBS中不含cm - plh(14.7±5.66)%)，细胞系依赖性（HEK293 > MCF-7 > COS7 > B16F10 > A549 > Hela > SPC-A1 > CHO > SKOV3）和孵育期依赖性（24小时、20小时、16小时> 12小时> 8小时> 4小时>小时> 1小时> 0.5小时）。负载pGV240-MDA-7/IL-24的复合纳米颗粒转染B16F10细胞后，由于IL-24的表达，B16F10细胞出现了明显的凋亡和增殖抑制。此外，在肺转移性黑色素瘤模型中，负载pGV240-MDA-7/IL-24的复合纳米颗粒在体内表现出显著的抗肿瘤治疗效果。这些结果表明，CM-PLH/ pbaa /pDNA三元复合纳米颗粒是具有实际应用前景和挑战性的基因载体。
To enhance serum-resistance and overcome the lysosomal barrier are effective and feasible strategies to increase the transfection efficiency of non-viral gene delivery system. For the systemic delivery of therapeutic gene, we previously developed self-assemble carboxymethyl poly(l-histidine) (CM-PLH)/poly(β-amino ester) (PbAE)/pDNA ternary complex nanoparticles based on electrostatic coating as an effective pDNA carrier. Recharging cationic PbAE/pDNA polyplexes with CM-PLH was a promising method to reduce the cytotoxicity and enhance the stabilityin vivoof positive charged polyplexes. In the present study, the transfection activities of ternary complex nanoparticles were further evaluatedin vitroandin vivo. The transfection efficiency of ternary complex nanoparticles showed significant serum-resistance (CM-PLH-containing (51.9 ± 4.35)% in 50% FBS > CM-PLH-free (14.7 ± 5.66)% in 50% FBS), cell line dependent (HEK293 > MCF-7 > COS7 > B16F10 > A549 > Hela > SPC-A1 > CHO > SKOV3) and incubation period dependent (24 h, 20 h, 16 h > 12 h > 8 h > 4 h > 2 h > 1 h > 0.5 h). After transfected with ternary complex nanoparticles loading pGV240-MDA-7/IL-24, the B16F10 cells exhibited significant apoptosis and proliferation inhibition due to the expression of IL-24. Moreover, in the pulmonary metastatic melanoma model, ternary complex nanoparticles loading pGV240-MDA-7/IL-24 showed significant antitumor therapeutic efficacyin vivo. These results suggested that CM-PLH/PbAE/pDNA ternary complex nanoparticles were promising and challenging gene vector for practical application.