College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China.
Research Center for Intelligent Sensing Systems, Zhejiang Lab, Hangzhou 311121, PR China.
Colloids Surf B Biointerfaces. 2023 Feb;222:113122. doi: 10.1016/j.colsurfb.2022.113122. Epub 2022 Dec 29.
Controllable size, self-degradability and targeting property are important for a precise improvement of anticancer effects and reduction of side effects of drug vehicles. Here, a series of DNA nanospheres with controllable size and self-degradation ability were constructed through the hybridization of two i-motif strands and two linker strands for targeted cancer therapy. DNA nanospheres with different sizes were fabricated by regulating the linker sequence, and their pH-responsive self-degradation property was realized by the introduction of the i-motif strand. Moreover, the ZY11 aptamer was introduced to endow the DNA nanospheres with targeting property toward SMMC-7721 cancer cells. The results revealed that the appropriate size of DNA nanospheres (80 nm) highly promoted the internalization by mammalian cells. The results of DLS, AFM and CD spectra showed that the DNA nanospheres were stable in a physiological environment but they self-degraded in a slightly acidic environment due to the existence of the i-motif strand. Moreover, the fluorescence of DOX@AP-NSs2 was triple at pH = 5.0 than at pH = 7.4, which further confirmed the pH-responsive drug release performance. The above results proved that the use of DOX@AP-NSs2 is a promising approach to accelerate the rapid release of drugs into the tumors and avoid drug leakage into the normal tissue. The results at a cellular level and in vivo confirmed the pH-responsive targeted antitumor effect. Hence, the novel DNA nanospheres with controllable size and self-degradable property represent a potential tool for targeted drug delivery and cancer therapy.
可控的尺寸、自降解性和靶向性对于精确提高抗癌效果和减少药物载体的副作用非常重要。在这里，通过杂交两条 i-motif 链和两条连接链构建了一系列具有可控尺寸和自降解能力的 DNA 纳米球，用于靶向癌症治疗。通过调节连接序列可以制备出不同尺寸的 DNA 纳米球，通过引入 i-motif 链实现了其 pH 响应性自降解特性。此外，还引入了 ZY11 适配体赋予 DNA 纳米球对 SMMC-7721 癌细胞的靶向性。结果表明，适当尺寸的 DNA 纳米球（80nm）可高度促进哺乳动物细胞的内化。DLS、AFM 和 CD 光谱的结果表明，DNA 纳米球在生理环境中是稳定的，但由于 i-motif 链的存在，它们在微酸性环境中会自行降解。此外，在 pH = 5.0 时，DOX@AP-NSs2 的荧光强度是在 pH = 7.4 时的三倍，这进一步证实了其 pH 响应性药物释放性能。上述结果证明，使用 DOX@AP-NSs2 是一种很有前途的方法，可以加速药物快速释放到肿瘤中，并避免药物泄漏到正常组织中。细胞水平和体内的结果证实了 pH 响应性靶向抗肿瘤作用。因此，具有可控尺寸和自降解性的新型 DNA 纳米球代表了一种用于靶向药物输送和癌症治疗的潜在工具。
