State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao, 066004, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
Chem Asian J. 2018 Nov 16;13(22):3526-3532. doi: 10.1002/asia.201800825. Epub 2018 Aug 16.
Organic photothermal sensitizers, such as indocyanine green (ICG), have been widely explored in photothermal therapy as a good substitute for inorganic materials owing to their advantageous biosafety and strong absorption in the near-infrared region. However, their intrinsic low stability and rapid clearance from the body requires further modification for efficient therapeutic application. In this work, we employed a covalent assembly strategy by covalently cross-linking genipin and a functional bola-amino acid to fabricate stable and degradable nanoparticles capable of loading ICG. The covalent assembly introduced strong covalent interactions in the assembly system together with functional linkers, which led to both enhanced stability and extended functionalities. This is distinguished from the conventional supramolecular strategy that relies only on weak noncovalent interactions. The functional building unit, consisting of phenylalanine and the disulfide bond, enables both good assembly and controllable degradation owing to the disulfide bond that responds to glutathione. The assembled nanoparticles show high stability, negligible toxicity, and considerable biodegradability. After loading ICG, the ICG-loaded nanoparticles possessed high photothermal conversion efficiency, and showed an enhanced photothermal effect in the near-infrared region. This covalent assembly strategy could be extended to various biomolecules containing a primary amino group for the fabrication of efficient and multifunctional nanomaterials used in biomedical applications.
有机光热敏化剂，如吲哚菁绿（ICG），由于其优越的生物安全性和在近红外区域的强吸收，已被广泛探索用于光热治疗，作为无机材料的良好替代品。然而，其内在的低稳定性和从体内快速清除需要进一步修饰，以实现有效的治疗应用。在这项工作中，我们采用共价组装策略，通过共价交联京尼平（genipin）和功能化的双（氨基酸）分子，制备了能够负载 ICG 的稳定且可降解的纳米粒子。共价组装在组装系统中引入了强共价相互作用和功能连接子，从而提高了稳定性和扩展了功能。这与仅依赖于弱非共价相互作用的传统超分子策略不同。由苯丙氨酸和二硫键组成的功能构建单元，由于二硫键对谷胱甘肽的响应，既能很好地组装，又能可控降解。组装的纳米粒子表现出高稳定性、低毒性和相当的可生物降解性。负载 ICG 后，负载 ICG 的纳米粒子具有高的光热转换效率，并在近红外区域显示出增强的光热效应。这种共价组装策略可以扩展到含有伯氨基的各种生物分子，用于制备用于生物医学应用的高效多功能纳米材料。
