Nagesetti Abhignyan, McGoron Anthony J
Biomedical Engineering Department, Florida International University, 10555 West Flagler Street, EC 2442, FL 33174, Miami, USA.
Biomedical Engineering Department, Florida International University, 10555 West Flagler Street, EC 2442, FL 33174, Miami, USA.
Colloids Surf B Biointerfaces. 2016 Nov 1;147:492-500. doi: 10.1016/j.colsurfb.2016.07.048. Epub 2016 Aug 18.
We report a novel system of organically modified silica nanoparticles (Ormosil) capable of near infrared fluorescence and chemotherapy with adjuvant hyperthermia for image guided cancer therapy. Ormosil nanoparticles were loaded with a chemotherapeutic, Doxorubicin (DOX) and cyanine dye, IR820. Ormosil particles had a mean diameter of 51.2±2.4 nanometers and surface charge of -40.5±0.8mV. DOX was loaded onto Ormosil particles via physical adsorption (FDSIR820) or covalent linkage (CDSIR820) to the silanol groups on the Ormosil surface. Both formulations retained DOX and IR820 over a period of 2 days in aqueous buffer, though CDSIR820 retained more DOX (93.2%) compared to FDSIR820 (77.0%) nanoparticles. Exposure to near infrared laser triggered DOX release from CDSIR820. Uptake of nanoparticles was determined by deconvolution microscopy in ovarian carcinoma cells (Skov-3). CDSIR820 localized in the cell lysosomes whereas cells incubated with FDSIR820 showed DOX fluorescence from the nucleus indicating leakage of DOX from the nanoparticle matrix. FDSIR820 nanoparticles showed severe toxicity in Skov-3 cells whereas CDSIR820 particles had the same cytotoxicity profile as bare (No DOX and IR820) Ormosil particles. Furthermore, exposure of CDSIR820 nanoparticles to Near Infrared laser at 808 nanometers resulted in generation of heat (to 43°C from 37°C) and resulted in enhanced cell killing compared to Free DOX treatment. Bio-distribution studies showed that CDSIR820 nanoparticles were primarily present in the organs of Reticuloendothelial (RES) system.
我们报告了一种新型的有机修饰二氧化硅纳米颗粒（Ormosil）系统，该系统能够实现近红外荧光成像、化疗并辅助热疗以用于图像引导的癌症治疗。Ormosil纳米颗粒负载了化疗药物阿霉素（DOX）和花菁染料IR820。Ormosil颗粒的平均直径为51.2±2.4纳米，表面电荷为-40.5±0.8毫伏。DOX通过物理吸附（FDSIR820）或共价连接（CDSIR820）负载到Ormosil表面的硅醇基团上。两种制剂在水性缓冲液中2天内都能保留DOX和IR820，不过与FDSIR820（77.0%）纳米颗粒相比，CDSIR820保留了更多的DOX（93.2%）。暴露于近红外激光会触发CDSIR820释放DOX。通过反卷积显微镜在卵巢癌细胞（Skov-3）中测定纳米颗粒的摄取情况。CDSIR820定位于细胞溶酶体中，而用FDSIR820孵育的细胞显示细胞核发出DOX荧光，表明DOX从纳米颗粒基质中泄漏。FDSIR820纳米颗粒在Skov-3细胞中显示出严重毒性，而CDSIR820颗粒具有与未负载（无DOX和IR820）的Ormosil颗粒相同的细胞毒性特征。此外，将CDSIR820纳米颗粒暴露于808纳米的近红外激光会产生热量（从37°C升至43°C），与游离DOX处理相比，导致细胞杀伤增强。生物分布研究表明，CDSIR820纳米颗粒主要存在于网状内皮系统（RES）的器官中。
