title: Tumor targeting and MR imaging with lipophilic cyanine-mediated near-infrared responsive porous Gd silicate nanoparticles.
abstract: We synthesize a NIR MHI-148 dye, a lipophilic heptamethine cyanine, with capability in tumor-targeting property to accumulate in the mitochondria of tumor. In the context of MHI-148 dye, we demonstrate effective tumor targeting and NIR fluorescence in vitro and in vivo for MHI-148 as compared to ICG. A series of porous Gd silicates related nanoparticles, i.e. Gd silicate, Gd silicate@mSiO(2) (mSiO(2): mesoporous silica shell), and Gd(3+)-chelated Gd silicate@mSiO(2) (Gd(3+)-DOTA chelated on the mSiO(2)) are fabricated to demonstrate their magnetic resonance (MR) contrast imaging effects. Those Gd silicates related nanoparticles exhibit dual MR effect, expressing T(1)-brightened and T(2)-darkened effects, in lower magnetic field. In high magnetic field, an abnormal enhanced transverse relaxivity (r(2)) appears, showing an effective T(2)-lowering effect, possibly due to concentrated Gd amount and porous architecture. The r(2) value increases 4-5 times as the field strength increased from 3T to 7T. The Gd(3+)-chelated Gd silicate@mSiO(2) has given large r(2) (T(2)-lowering effect) up to 343.8 s(-1) mM(-1), which is even larger than the reported magnetic Fe(3)O(4) nanoparticles measured at the same field. Using a 9.4T animal micro MRI system we have seen effectively darken in signal for those porous Gd silicates related NPs, while no such phenomenon appears in commercial Gd-DOTA agent. The MHI-148 is then conjugated on the porous Gd silicate@mSiO(2) nanoparticles for a new paradigm with three functionalities for in vivo tumor targeting, near-infrared fluorescent and MR imaging by means of only using MHI-148 dye.
authors: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan. csyeh@mail.ncku.edu.tw
authors: Chen-Sheng
authors: CS
authors: Yeh
authors: Chia-Hao
authors: CH
authors: Su
authors: Wen-Yueh
authors: WY
authors: Ho
authors: Chih-Chia
authors: CC
authors: Huang
authors: Jui-Cheng
authors: JC
authors: Chang
authors: Yi-Hsin
authors: YH
authors: Chien
authors: Shu-Ting
authors: ST
authors: Hung
authors: Min-Chiau
authors: MC
authors: Liau
authors: Hsin-Yi
authors: HY
authors: Ho
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D004705:Endocytosis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005453:Fluorescence; D005682:Gadolinium; D006571:Heterocyclic Compounds; D006801:Humans; D007208:Indocyanine Green; D008055:Lipids / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism*; D009928:Organ Specificity; D009942:Organometallic Compounds; D016062:Porosity; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D017640:Silicates; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors
chemical_list: D002232:Carbocyanines; D006571:Heterocyclic Compounds; D008055:Lipids; D009942:Organometallic Compounds; D011437:Propylamines; D012821:Silanes; D017640:Silicates; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium; D007208:Indocyanine Green; C477625:amino-propyl-triethoxysilane