Martín-Saavedra Francisco, Vilaboa Nuria
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain.
Edificio de Investigación, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046, Madrid, Spain.
Methods Mol Biol. 2016;1408:281-92. doi: 10.1007/978-1-4939-3512-3_19.
The development of noninvasive technologies for remote control of gene expression has received increased attention for their therapeutic potential in clinical scenarios, including cancer, neurological disorders, immunology, tissue engineering, as well as developmental biology research. Near-infrared (NIR) light is a suitable source of energy that can be employed to pattern transgene expression in plasmonic cell constructs. Gold nanoparticles tailored to exhibit a plasmon surface band absorption peaking at NIR wavelengths within the so called tissue optical window (TOW) can be used as fillers in fibrin-based hydrogels. These biocompatible composites can be loaded with cells harboring heat-inducible gene switches. NIR laser irradiation of the resulting plasmonic cell constructs causes the local conversion of NIR photon energy into heat, achieving spatially restricted patterns of transgene expression that faithfully match the illuminated areas of the hydrogels. In combination with cells genetically engineered to harbor gene switches activated by heat and dependent on a small-molecule regulator (SMR), NIR-responsive hydrogels allow reliable and safe control of the spatiotemporal availability of therapeutic biomolecules in target tissues.
用于远程控制基因表达的非侵入性技术的发展因其在临床场景中的治疗潜力而受到越来越多的关注，这些临床场景包括癌症、神经疾病、免疫学、组织工程以及发育生物学研究。近红外（NIR）光是一种合适的能量来源，可用于在等离子体细胞构建体中对转基因表达进行图案化。定制为在所谓的组织光学窗口（TOW）内的近红外波长处表现出等离子体表面带吸收峰值的金纳米颗粒可作为基于纤维蛋白的水凝胶中的填料。这些生物相容性复合材料可以装载带有热诱导基因开关的细胞。对所得的等离子体细胞构建体进行近红外激光照射会导致近红外光子能量局部转化为热量，从而实现与水凝胶照射区域忠实匹配的转基因表达的空间受限图案。与经过基因工程改造以携带由热激活并依赖小分子调节剂（SMR）的基因开关的细胞相结合，近红外响应水凝胶能够可靠且安全地控制治疗性生物分子在靶组织中的时空可用性。
