Nanomicelles,self-assembling nanosized particles with a hydrophobic core and hydrophilic shell,are currently successfully used as carriers for targeted drug delivery systems via the enhanced permeability and retention...Nanomicelles,self-assembling nanosized particles with a hydrophobic core and hydrophilic shell,are currently successfully used as carriers for targeted drug delivery systems via the enhanced permeability and retention（EPR） effect at the tumor sites.In this study,a near-infrared fluorescent cyanine dye（Cy7-NHS） was conjugated to poly（ethylene glycol）-block-poly（ε-caprolactone）（NH 2-PEG-b-PCL）,and the resulting Cy7-PEG-PCL was further mixed with mPEG-b-PCL to form nanomicelles as carriers for paclitaxel（PTX） delivery.Our results showed that the selected mPEG 4000-b-PCL 2500 copolymers self-assembled to form stable micelles with an average size of 30 nm in diameter and a zeta potential of approximately-3 mV.The micelles also exhibited more than 95% encapsulation efficiency of PTX when the molar ratio between paclitaxel and copolymers was 1/4.In vitro cytotoxicity study showed that the PTX-loaded nanomicelles had a similar cell growth inhibition efficacy to that of Taxol against human breast cancer MCF-7 cells.In vivo imaging showed that the Cy7-labeled nanomicelles could be passively targeted to tumor sites effectively after intravenous injection via the tail vein.Also,a strong anti-tumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treatment with PTX-loaded micelles,similar to that of Taxol.As a result,the micelle drug delivery system designed in this paper has great potential in targeted imaging of tumors and chemotherapy.展开更多
Lamellar crystals of diblock, triblock and four-arm poly（ethylene glycol）-b-poly（ε-caprolactone） （PEG-b-PCL） crystalline-crystalline copolymers were successfully obtained from their solution. Morphology and str...Lamellar crystals of diblock, triblock and four-arm poly（ethylene glycol）-b-poly（ε-caprolactone） （PEG-b-PCL） crystalline-crystalline copolymers were successfully obtained from their solution. Morphology and structure of lamellar crystals of crystalline-crystalline copotymers were investigated using tapping-mode atomic force microscopy （AFM） and selected area electron diffraction （SAED）. All of these samples showed the truncated-lozenge multilayer basal shapes with central screw dislocation or central stack, which were all obtained simultaneously from the oil bath. The diffraction pattern of PEG block lamellar crystal is attributed to the （120） diffracting planes and the pattern of PCL block lamellar crystal is attributed to the （1 I0） diffracting planes and （200） diffracting planes according to the SAED results. Four （110） crystal growth planes and two （200） crystal growth planes are discovered for the PCL blocks, but the （120） crystal growth planes of PEG blocks are hided in the figure of AFM. The crystalline structure of the four-arm copolymers （FA） is more disorder and confused than that of the diblock （DI） copolymer and the striated fold surface structures of lamellar crystals of four-arm copolymers （FA） are smoother than these of linear analogues, owing to the confused crystallization of blocks caused by the mutual restriction of blocks and the hindrance of the dendritic cores. In addition, the aspect ratio of FA is greater than that of the others. It is hypothesized that there are two reasons for the change of aspect ratios. First, the （200） diffracting planes of PCL crystals grew slowly compared to their （110） diffracting planes because of difference in the energy barrier. Secondly, edge dislocations on the （200） diffracting planes are also responsible for the variation of the aspect ratio. Consequently, the crystalline defects are augmented by the competing blocks crystallized simultaneously and the hindrance of the dendritic cores.展开更多
基金National Basic Research Program of China (973Program,Grant No. 2007CB935800 and 2009CB930300)Program forNew Drug R&D (Grant No. 2009ZX09310-001)+2 种基金NSFC projects(Grant No. 81072597)Beijing NSF project (Grant No. 7112089)Programs from Ministry of Education (Grant No. BMU20110268and BMU20110263)
文摘Nanomicelles,self-assembling nanosized particles with a hydrophobic core and hydrophilic shell,are currently successfully used as carriers for targeted drug delivery systems via the enhanced permeability and retention（EPR） effect at the tumor sites.In this study,a near-infrared fluorescent cyanine dye（Cy7-NHS） was conjugated to poly（ethylene glycol）-block-poly（ε-caprolactone）（NH 2-PEG-b-PCL）,and the resulting Cy7-PEG-PCL was further mixed with mPEG-b-PCL to form nanomicelles as carriers for paclitaxel（PTX） delivery.Our results showed that the selected mPEG 4000-b-PCL 2500 copolymers self-assembled to form stable micelles with an average size of 30 nm in diameter and a zeta potential of approximately-3 mV.The micelles also exhibited more than 95% encapsulation efficiency of PTX when the molar ratio between paclitaxel and copolymers was 1/4.In vitro cytotoxicity study showed that the PTX-loaded nanomicelles had a similar cell growth inhibition efficacy to that of Taxol against human breast cancer MCF-7 cells.In vivo imaging showed that the Cy7-labeled nanomicelles could be passively targeted to tumor sites effectively after intravenous injection via the tail vein.Also,a strong anti-tumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treatment with PTX-loaded micelles,similar to that of Taxol.As a result,the micelle drug delivery system designed in this paper has great potential in targeted imaging of tumors and chemotherapy.
基金the National Natural Science Foundation of China(Nos.21004073 and 51003117)Zhejiang Province Innovative Research Team(No.2009R50013)+2 种基金Ningbo Innovative Research Team(No.2009B21008)Ningbo Key Lab of Polymer Materials(No.2010A22001)Zhejiang Provincial Natural Science Foundation(No.Y4100517)
文摘Lamellar crystals of diblock, triblock and four-arm poly（ethylene glycol）-b-poly（ε-caprolactone） （PEG-b-PCL） crystalline-crystalline copolymers were successfully obtained from their solution. Morphology and structure of lamellar crystals of crystalline-crystalline copotymers were investigated using tapping-mode atomic force microscopy （AFM） and selected area electron diffraction （SAED）. All of these samples showed the truncated-lozenge multilayer basal shapes with central screw dislocation or central stack, which were all obtained simultaneously from the oil bath. The diffraction pattern of PEG block lamellar crystal is attributed to the （120） diffracting planes and the pattern of PCL block lamellar crystal is attributed to the （1 I0） diffracting planes and （200） diffracting planes according to the SAED results. Four （110） crystal growth planes and two （200） crystal growth planes are discovered for the PCL blocks, but the （120） crystal growth planes of PEG blocks are hided in the figure of AFM. The crystalline structure of the four-arm copolymers （FA） is more disorder and confused than that of the diblock （DI） copolymer and the striated fold surface structures of lamellar crystals of four-arm copolymers （FA） are smoother than these of linear analogues, owing to the confused crystallization of blocks caused by the mutual restriction of blocks and the hindrance of the dendritic cores. In addition, the aspect ratio of FA is greater than that of the others. It is hypothesized that there are two reasons for the change of aspect ratios. First, the （200） diffracting planes of PCL crystals grew slowly compared to their （110） diffracting planes because of difference in the energy barrier. Secondly, edge dislocations on the （200） diffracting planes are also responsible for the variation of the aspect ratio. Consequently, the crystalline defects are augmented by the competing blocks crystallized simultaneously and the hindrance of the dendritic cores.
