Key Laboratory of Advanced Technologies of Materials Ministry of Education of China, School of Materials Science & Engineering, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
Pharm Res. 2012 Aug;29(8):2167-79. doi: 10.1007/s11095-012-0745-1. Epub 2012 Apr 5.
Biodegradable polymers containing acid-labile segments and galactose grafts were formulated into nanoparticles in current study, and enhanced cellular uptake and subcellular distribution were clarified.
Quantum dots (QDs) was utilized as an imaging agent and a model of bioactive substances, and entrapped into nanoparticles of around 200 nm through a nanoprecipitation process.
The acid-labile characteristics of QDs-loaded nanoparticles were approved by the hemolysis capability, the degradation behaviors of matrix polymers, and the fluorescence decay of entrapped QDs after incubation into buffer solutions of different pH values. The galactose grafts increased the acid-lability, due to the hydrophilic moieties on the acid-labile segments, and enhanced uptake efficiency of over 50 % was found after 4 h incubation with HepG2 cells, due to the galactose-receptor mediated endocytosis. The acid-lability led to an efficient endosomal escape of QDs-loaded nanoparticles into cytoplasm.
The integration of acid-lability, targeting effect, and full biodegradable backbone into nanoparticle matrices constitutes a promising platform for intracellular delivery of bioactive substances for disease diagnosis, imaging and treatment.
本研究中将含有酸敏感片段和半乳糖接枝的可生物降解聚合物制成纳米粒子，并阐明了其增强的细胞摄取和亚细胞分布。
量子点（QDs）被用作成像剂和生物活性物质的模型，并通过纳米沉淀过程包封在约 200nm 的纳米粒子中。
通过测定血红蛋白溶血能力、基质聚合物的降解行为以及在不同 pH 值的缓冲溶液中孵育后包封的 QDs 的荧光衰减，证实了载量子点纳米粒子的酸敏感性。由于酸敏感片段上的亲水部分，半乳糖接枝增加了酸敏感性，并且在与 HepG2 细胞孵育 4 小时后，发现摄取效率提高了 50%以上，这是由于半乳糖受体介导的内吞作用。酸敏感性导致载量子点纳米粒子有效地从内涵体逃逸到细胞质中。
将酸敏感性、靶向效应和完全可生物降解的骨架整合到纳米粒子基质中，为疾病诊断、成像和治疗的生物活性物质的细胞内递供了一个有前途的平台。
