Department of Science Education, National Taipei University of Education, No.134, Sec. 2, Heping E. Rd., Da-an District, Taipei City 106, Taiwan.
School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City 110, Taiwan.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110593. doi: 10.1016/j.msec.2019.110593. Epub 2019 Dec 27.
Giving patients right dosage is an essential concept of precision medicine. Most of nanocarriers lack of flexible drug capacity and structural stability to be customized for specific treatment, resulting in low therapeutic efficacy and unexpected side effects. Thus, a growing need emerges for fast and rigorous approaches to develop nanoparticles with properties of adjustable dosage and controllable particle size. Poly-l-Lysine is known for its enhanced bioadhesivity and pH-triggered structural swelling effect, which is utilized as the main agent to activate the multistage drug releasing. Inspired by natural bio-assembly system, we report a simple method to self-assemble Poly-l-Lysine-based nanoparticles via supramolecular recognitions of cross-linked pyrenes, which provides noncovalent force to flexibly encapsulate Doxorubincin and to construct robust nanostructures. Pyrene-modified polypeptide self-assemblies are able to adjust drug payload from 1: 10 to 2:1 (drug: polypeptide) without changing its uniform nano-spherical morphology. This nanostructure remained the as-made morphology even after experiencing the long-term (~ 10 weeks) storage at room temperature. Also, the nanoparticles displayed multi-step drug release behaviours and exhibited great in vitro and in vivo cytotoxicity towards colon cancer cells. The as-mentioned nanoparticles provide a novel perspective to compensate the clinical needs of specific drug feedings and scalable synthesis with advantages of simple-synthesis, size-adaptivity, and morphology reversibility.
给患者正确的剂量是精准医学的一个基本概念。大多数纳米载体缺乏灵活的药物容量和结构稳定性，无法针对特定的治疗进行定制，导致治疗效果低和意想不到的副作用。因此，迫切需要快速和严格的方法来开发具有可调节剂量和可控粒径的纳米粒子。聚-L-赖氨酸因其增强的生物粘附性和 pH 触发的结构溶胀效应而被用作主要试剂来激活多阶段药物释放。受天然生物组装系统的启发，我们报告了一种通过交联苝的超分子识别来自组装基于聚-L-赖氨酸的纳米粒子的简单方法，该方法提供了非共价力来灵活地包封阿霉素并构建坚固的纳米结构。芘修饰多肽自组装能够在不改变其均匀纳米球形形态的情况下，将药物载量从 1:10 调节至 2:1（药物：多肽）。即使在室温下长期（约 10 周）储存后，这种纳米结构仍保持原始形态。此外，这些纳米粒子表现出多步药物释放行为，并对结肠癌细胞表现出优异的体外和体内细胞毒性。所述纳米粒子提供了一种新的视角，可以弥补特定药物喂养的临床需求，并具有合成简单、尺寸适应性和形态可逆性的优势。
