title: Near-Infrared Light Activation of Proteins Inside Living Cells Enabled by Carbon Nanotube-Mediated Intracellular Delivery.
abstract: Light-responsive proteins have been delivered into the cells for controlling intracellular events with high spatial and temporal resolution. However, the choice of wavelength is limited to the UV and visible range; activation of proteins inside the cells using near-infrared (NIR) light, which has better tissue penetration and biocompatibility, remains elusive. Here, we report the development of a single-walled carbon nanotube (SWCNT)-based bifunctional system that enables protein intracellular delivery, followed by NIR activation of the delivered proteins inside the cells. Proteins of interest are conjugated onto SWCNTs via a streptavidin-desthiobiotin (SA-DTB) linkage, where the protein activity is blocked. SWCNTs serve as both a nanocarrier for carrying proteins into the cells and subsequently a NIR sensitizer to photothermally cleave the linkage and release the proteins. The released proteins become active and exert their functions inside the cells. We demonstrated this strategy by intracellular delivery and NIR-triggered nuclear translocation of enhanced green fluorescent protein, and by intracellular delivery and NIR-activation of a therapeutic protein, saporin, in living cells. Furthermore, we showed that proteins conjugated onto SWCNTs via the SA-DTB linkage could be delivered to the tumors, and optically released and activated by using NIR light in living mice.
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking-Tsinghua Center for Life Sciences, Peking University , Beijing 100871, China.
authors: He
authors: H
authors: Li
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking-Tsinghua Center for Life Sciences, Peking University , Beijing 100871, China.
authors: Xinqi
authors: X
authors: Fan
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking-Tsinghua Center for Life Sciences, Peking University , Beijing 100871, China.
authors: Xing
authors: X
authors: Chen
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000187:drug effects; D016503:Drug Delivery Systems; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007259:Infrared Rays; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D019809:Streptavidin / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D037742:Nanotubes, Carbon; D011506:Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001710:Biotin; C004749:desthiobiotin; D019809:Streptavidin
keywords: bionanotechnology; near-infrared light; protein activation; protein delivery; spatiotemporal control