Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, People's Republic of China.
J Nanobiotechnology. 2021 Feb 24;19(1):54. doi: 10.1186/s12951-020-00759-3.
Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.
In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.
The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
在过去的二十年中，基因和化学疗法已成为分子医学领域的新兴领域之一。然而，在开发高效、靶向且安全的输送系统方面仍然存在许多挑战，这些系统可以避免 siRNA 降解并降低化疗药物的毒性和不良反应。
本文提出了一种高效的 AS1411 适体修饰、dsDNA 和 MMP-2 可切割肽制备的金纳米笼载体，可装载盐酸阿霉素（DOX）和 siRNAs，实现肿瘤响应性基因治疗、化学治疗和光热治疗的联合。我们的结果表明，这种联合治疗实现了靶向基因沉默和肿瘤抑制。在用 DOX 负载的 Au-siRNA-PAA-AS1411 纳米粒子进行治疗近一个月后，每隔三天给药一次，在小鼠中观察到协同作用促进了长寿肿瘤的消除，并且小鼠的存活率增加。与被动基因治疗组的 30%肿瘤抑制率和 0%存活率相比，联合基因、化学治疗和光热治疗组的肿瘤抑制率超过 90%（肿瘤信号），存活率约为 67%。
具有双链 DNA 和 MMP-2 可切割肽的纳米载体的开发为基因和化疗药物的联合递送提供了一种新策略。Au-siRNA-PAA-AS1411 对肺癌表现出高抗癌活性，表明其在临床应用方面具有巨大潜力。
