Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu, Taiwan.
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Taiwan.
J Control Release. 2020 May 10;321:159-173. doi: 10.1016/j.jconrel.2020.02.018. Epub 2020 Feb 8.
Compact nanohybrids can potentially unite various therapeutic features and reduce side effects for precise cancer therapy. However, the poor accumulation and limited tumor penetration of drugs at the tumor impede the manifestation of nanomedicine. We developed a rabies virus glycoprotein (RVG)-amplified hierarchical targeted hybrid that acts as a stealthy and magnetolytic carrier that transports dual tumor-penetrating agents incorporating two drugs (boron-doped graphene quantum dots (B-GQDs)/doxorubicin and pH-responsive dendrimers (pH-Den)/palbociclib). The developed RVG-decorated hybrids (RVG-hybrids) enhance the accumulation of drugs at tumor by partially bypassing the BBB via spinal cord transportation and pH-induced aggregation of hierarchical targeting. The penetrated delivery of dual pH-Den and B-GQD drugs to deep tumors is actuated by magnetoelectric effect, which are able to generate electrons to achieve electrostatic repulsion and disassemble the hybrids into components of a few nanometers in size. The synergy of magnetoelectric drug penetration and chemotherapy was achieved by delivery of the B-GQDs and pH-Den to orthotopic tumors, which prolonged the host survival time. This RVG-amplified dual hierarchical delivery integrated with controlled and penetrated release from this hybrid improve the distribution of the therapeutic agents at the brain tumor for synergistic therapy, exhibiting potential for clinic use.
紧凑型纳米杂化体能将各种治疗特性结合起来，并减少副作用，实现精确的癌症治疗。然而，药物在肿瘤处的蓄积不良和有限的肿瘤穿透性阻碍了纳米医学的表现。我们开发了一种狂犬病病毒糖蛋白 (RVG) 扩增的分级靶向杂化体，作为一种隐形和磁解的载体，可输送包含两种药物（硼掺杂石墨烯量子点 (B-GQDs)/阿霉素和 pH 响应树枝状聚合物 (pH-Den)/哌柏西利）的双肿瘤穿透剂。开发的 RVG 修饰的杂化体（RVG-杂化体）通过脊髓转运部分绕过 BBB，并通过 pH 诱导的分级靶向聚集增强药物在肿瘤处的蓄积。双 pH-Den 和 B-GQD 药物的穿透递送由磁电效应驱动，该效应能够产生电子以实现静电排斥，并将杂化体分解为几个纳米大小的组件。通过将 B-GQDs 和 pH-Den 递送到原位肿瘤，实现了磁电药物穿透和化疗的协同作用，延长了宿主的生存时间。这种 RVG 扩增的双重分级递药与从该杂化体中进行的受控和穿透性释放相结合，改善了脑肿瘤中治疗剂的分布，实现了协同治疗，具有临床应用的潜力。
