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Focused ultrasound-triggered chemo-gene therapy with multifunctional nanocomplex for enhancing therapeutic efficacy.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.jconrel.2020.03.041 Hyounkoo Han 1 , Doyeon Kim 1 , Yongho Jang 1 , Minkyu Seo 1 , Kwangmeyung Kim 2 , Jong Bum Lee 3 , Hyuncheol Kim 4
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.jconrel.2020.03.041 Hyounkoo Han 1 , Doyeon Kim 1 , Yongho Jang 1 , Minkyu Seo 1 , Kwangmeyung Kim 2 , Jong Bum Lee 3 , Hyuncheol Kim 4
Affiliation
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Nanotechnology-based combination therapies, especially chemo-gene therapy, have been spotlighted as promising alternatives for cancer therapy. However, only a small amount of systemically administered nanomedicines reach the tumor site by the enhanced permeability and retention (EPR) effect, resulting in the limited therapeutic efficacy. Furthermore, the design of ideal drug delivery system for chemo-gene therapy has been impeded by the chemical and physical differences between nucleic acids and chemotherapeutics. Herein, we report a precisely designed nanocomplex which exhibits a focused ultrasound (FU)-responsive release and enhanced accumulation of released therapeutics to tumor site. After the nanocomplex composed of siRNA nanoparticles (siRNA-NP) and chemotherapeutics-loaded microbubbles was systemically injected, the nanocomplex was collapsed around the tumor tissue by FU exposure, and both siRNA-NP and chemotherapeutics were penetrated the dense extracellular matrix (ECM) of tumor site, leading to the enhanced chemo-gene therapeutic efficacy. The two-in-one nanocomplex is expected as a promising platform for combination therapy that can enhance the therapeutic efficiency of combination drugs at the cell and/or tissue levels with high drug loading ratio.
中文翻译：
具有多功能纳米复合物的聚焦超声触发化学基因治疗以提高治疗效果。
基于纳米技术的联合疗法，尤其是化学基因疗法，已成为癌症治疗的有希望的替代方案。然而，只有少量全身给药的纳米药物通过增强通透性和保留（EPR）效应到达肿瘤部位，导致治疗效果有限。此外，用于化学基因治疗的理想药物递送系统的设计受到核酸和化学治疗剂之间的化学和物理差异的阻碍。在这里，我们报告了一种精确设计的纳米复合物，它表现出聚焦超声 (FU) 响应释放和释放的治疗剂对肿瘤部位的增强积累。在全身注射由siRNA纳米粒子（siRNA-NP）和装载化疗药物的微泡组成的纳米复合物后，通过 FU 暴露，纳米复合物在肿瘤组织周围塌陷，siRNA-NP 和化疗药物都穿透肿瘤部位的致密细胞外基质 (ECM)，从而增强了化疗基因的治疗效果。二合一纳米复合物有望成为一种有前途的联合治疗平台，可以提高联合药物在细胞和/或组织水平上的治疗效率，并具有高载药率。
更新日期：2020-04-01
中文翻译：
具有多功能纳米复合物的聚焦超声触发化学基因治疗以提高治疗效果。
基于纳米技术的联合疗法，尤其是化学基因疗法，已成为癌症治疗的有希望的替代方案。然而，只有少量全身给药的纳米药物通过增强通透性和保留（EPR）效应到达肿瘤部位，导致治疗效果有限。此外，用于化学基因治疗的理想药物递送系统的设计受到核酸和化学治疗剂之间的化学和物理差异的阻碍。在这里，我们报告了一种精确设计的纳米复合物，它表现出聚焦超声 (FU) 响应释放和释放的治疗剂对肿瘤部位的增强积累。在全身注射由siRNA纳米粒子（siRNA-NP）和装载化疗药物的微泡组成的纳米复合物后，通过 FU 暴露，纳米复合物在肿瘤组织周围塌陷，siRNA-NP 和化疗药物都穿透肿瘤部位的致密细胞外基质 (ECM)，从而增强了化疗基因的治疗效果。二合一纳米复合物有望成为一种有前途的联合治疗平台，可以提高联合药物在细胞和/或组织水平上的治疗效率，并具有高载药率。
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