Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Key Lab of Resource Chemistry of MOE & Shanghai Key Lab of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China.
J Inorg Biochem. 2022 Jan;226:111656. doi: 10.1016/j.jinorgbio.2021.111656. Epub 2021 Nov 9.
A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.
多功能纳米平台 APIPB-MnCO@TPP@N,P-GQDs（APIPB=N-(2-氨基苯基)-4-(1H-咪唑并[4,5-f][1,10]菲咯啉-2-基)苯甲酰胺，TPP=三苯基膦，Mn=锰，CO=一氧化碳，GQDs=石墨烯量子点），纳米平台（1），被合成，其由荧光 N、P 掺杂的 GQDs 载体组成，其表面通过具有组蛋白去乙酰化酶（HDAC）抑制特性的 CO 供体 APIPB-MnCO 和导向基团 TPP 衍生物共价功能化。纳米平台（1）选择性地定位于 HeLa 细胞的线粒体，以抑制 HDAC 活性，并在 808nm 近红外光照射下释放 CO，破坏线粒体并诱导癌细胞凋亡。靶向亚细胞线粒体 CO 传递与抑制 HDAC 活性相结合，最大限度地提高了纳米平台的细胞毒性，这可能为 CO 介导的癌症治疗多模态治疗提供新的见解。
