CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety , National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences , Beijing 100190 , China.
J Am Chem Soc. 2019 Mar 13;141(10):4406-4411. doi: 10.1021/jacs.8b13512. Epub 2019 Mar 5.
The precise and highly efficient drug delivery of nanomedicines into lesions remains a critical challenge in clinical translational research. Here, an autocatalytic morphology transformation platform is presented for improving the tumor-specific accumulation of drugs by kinetic control. The in situ reorganization of prodrug from nanoparticle to β-sheet fibrous structures for targeted accumulation is based on nucleation-based growth kinetics. During multiple administrations, the autocatalytic morphology transformation can be realized for skipping slow nucleating process and constructing the bulky nanoassembly instantaneously, which has been demonstrated to induce the cumulative effect of prodrug. Furthermore, the sustained drug release from fibrous prodrug depot in the tumor site inhibits the tumor growth efficiently. The autocatalytic morphology transformation strategy in vivo offers a novel perspective for targeted delivery strategy by introducing chemical kinetics and shows great potential in disease theranostics.
纳米药物在病变部位的精确高效递药仍然是临床转化研究中的一个关键挑战。在这里,提出了一种自动催化形态转变平台,通过动力学控制来提高药物的肿瘤特异性积累。基于成核生长动力学,药物前体从纳米颗粒原位重组为β-片状纤维结构以实现靶向积累。在多次给药过程中,可以实现自动催化形态转变,跳过缓慢的成核过程,瞬间构建大体积纳米组装体,从而诱导药物前体的累积效应。此外,纤维状药物前体库在肿瘤部位的持续药物释放可以有效地抑制肿瘤生长。体内的自动催化形态转变策略通过引入化学动力学为靶向递药策略提供了新的视角,并在疾病治疗学中显示出巨大的应用潜力。