Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a t...Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.展开更多
文摘Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.
基金The authors would like to thank Prof. Feng Wang, Prof. Xuedong Bai, and Prof. Kaihui Liu for helpful discussions. This work was supported by the National Basic Research Program of China （No. 2012CB932301） and the National Natural Science Foundation of China （Nos. 90921012, 11321091, 51102144, 11274190, and 51102147）.
