Center for Molecular Recognition and Biosensing, School of Life Sciences , Shanghai University , Shanghai 200444 , P. R. China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200032 , P. R. China.
ACS Nano. 2019 Jun 25;13(6):7333-7344. doi: 10.1021/acsnano.9b03846. Epub 2019 Jun 12.
A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations in the range of ∼5.0-7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli-responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy.
已经开发出一种基于 DNA 的刺激响应型药物输送系统，用于协同癌症治疗。该系统建立在三联体 DNA 纳米开关上，能够精确响应 pH 值在约 5.0-7.0 范围内的变化。在细胞外中性 pH 空间中，DNA 纳米开关保持线性构象，同时固定多种治疗剂，如小分子和反义化合物。通过内吞作用靶向摄取癌细胞后，纳米开关在酸性细胞内隔室中经历从线性到三联体的构象变化，导致治疗组合的智能释放。这种刺激响应型药物输送系统不依赖于人工响应材料，因此具有生物相容性。此外，它还能够同时输送多种治疗剂以提高疗效。通过使用荷瘤小鼠模型，我们展示了在静脉注射智能纳米开关后有效的基因沉默和显著的肿瘤生长抑制，为组合癌症治疗提供了机会。
