Department of Chemistry , Paderborn University , Warburger Str. 100 , D-33098 Paderborn , Germany.
School of Polymer Science and Engineering , Qingdao University of Science and Technology , Zhengzhou Rd. 53 , CN-266042 Qingdao , China.
Biomacromolecules. 2018 Dec 10;19(12):4677-4690. doi: 10.1021/acs.biomac.8b01446. Epub 2018 Nov 29.
Aliphatic poly(carbonate)s (APCs) with rapid and controlled degradation upon specific stimulation have great advantages for a variety of biomedical and pharmaceutical applications. In the present work, we reported a new poly(trimethylene carbonate) (PTMC)-based copolymer containing multiple 4,5-dimethoxy-2-nitrobenzyl photo cleavable groups as pendent chains. The six-membered light-responsive cyclic carbonate monomer (LrM) was first prepared from 2-(hydroxymethyl)-2-methylpropane-1,3-diol and 4,5-dimethoxy-2-nitrobenzyl alcohol and then copolymerized with trimethylene carbonate (TMC) by 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) catalyzed ring-opening polymerization (ROP) to afford the light-responsive polycarbonate (LrPC). The light-triggered decomposition of LrM and LrPC was studied by NMR, UV/vis spectroscopy, and size exclusion chromatography (SEC), as well as ESI-ToF mass spectrometry. Stable monodisperse nanoparticles with hydrodynamic diameter of 100 nm could be formulated from 25% LrPC and 75% poly(lactide- co-glycolide) (PLGA) and applied for the encapsulation of temoporfin. Upon irradiation with UV light these particles displayed a significant decrease of the particle countrate and increased the release rate of temoporfin in comparison to standard PLGA nanoparticles. This work demonstrated that a combination of encapsulation of photosensitizer and light degradation using light-responsive polymers is suitable to enhance photodynamic therapy (PDT).
具有特定刺激下快速可控降解的脂肪族聚碳酸酯（APCs）在各种生物医学和药物应用中具有巨大优势。在本工作中，我们报道了一种新型的含多个 4,5-二甲氧基-2-硝基苄基光裂解基团作为侧链的聚（三亚甲基碳酸酯）（PTMC）共聚物。六元光响应环碳酸酯单体（LrM）首先由 2-（羟甲基）-2-甲基丙烷-1,3-二醇和 4,5-二甲氧基-2-硝基苄醇制备，然后通过 1,8-二氮杂二环[5.4.0]十一碳-7-烯（DBU）催化开环聚合（ROP）与三亚甲基碳酸酯（TMC）共聚得到光响应性聚碳酸酯（LrPC）。通过 NMR、UV/vis 光谱、尺寸排阻色谱（SEC）和 ESI-ToF 质谱研究了 LrM 和 LrPC 的光触发分解。可以从 25%的 LrPC 和 75%的聚（乳酸-共-羟基乙酸）（PLGA）配制出具有 100nm 流体动力学直径的稳定单分散纳米粒子，并用于封装替莫泊芬。与标准 PLGA 纳米粒子相比，这些粒子在紫外光照射下显示出粒子计数率显著降低和替莫泊芬释放速率增加。这项工作表明，使用光响应聚合物封装光敏剂和光降解的结合适用于增强光动力疗法（PDT）。
