Applied Chemistry Department, College of Material Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211100, China.
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Small. 2018 Dec;14(52):e1803952. doi: 10.1002/smll.201803952. Epub 2018 Nov 19.
The targeting ability, drug-loading capacity, and size of the drug nanocarriers are crucial for enhancing the therapeutic index for cancer therapy. Herein, the morphology and size-controllable fabrication of supramolecular tumor-targeting nanocarriers based on host-guest recognition between a novel pillar[5]arene-based prodrug WP5-DOX and a Arg-Gly-Asp (RGD)-modified sulfonate guest RGD-SG is reported. The amphiphilic WP5-DOX⊃RGD-SG complex with a molar ratio of 5:1 self-assembles into vesicles, whereas smaller-sized micelles can be obtained by changing the molar ratio to 1:3. This represents a novel strategy of controllable construction of supramolecular nanovehicles with different sizes and morphologies based on the same host-guest interactions by using different host-guest ratios. Furthermore, in vitro and in vivo studies reveal that both these prodrug nanocarriers could selectively deliver doxorubicin to RGD receptor-overexpressing cancer cells, leading to longer blood retention time, enhanced antitumor efficacy, and reduced systematic toxicity in murine tumor model, suggesting their potential application for targeted drug delivery.
靶向能力、载药量和药物纳米载体的大小对于提高癌症治疗的治疗指数至关重要。在此，报告了基于新型基于柱[5]芳烃的前药 WP5-DOX 与 Arg-Gly-Asp（RGD）修饰的磺酸盐客体 RGD-SG 之间的主客体识别，构建形态和尺寸可控的超分子肿瘤靶向纳米载体。摩尔比为 5:1 的两亲性 WP5-DOX⊃RGD-SG 复合物自组装成囊泡，而通过改变摩尔比为 1:3 可以得到更小尺寸的胶束。这代表了一种基于相同主客体相互作用，通过使用不同的主客体比，可控构建具有不同尺寸和形态的超分子纳米载体的新策略。此外，体外和体内研究表明，这两种前药纳米载体都可以选择性地将阿霉素递送到 RGD 受体过表达的癌细胞中，导致更长的血液保留时间，增强抗肿瘤功效，并降低小鼠肿瘤模型中的系统毒性，表明它们在靶向药物递送方面的潜在应用。
