| Title |
Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer
|
|---|---|
| Published in |
International Journal of Nanomedicine, July 2015
|
| DOI | 10.2147/ijn.s84930 |
| Pubmed ID | |
| Authors |
Qingbing Wang, Jianfeng Li, Sai An, Yi Chen, Chen Jiang, Xiaolin Wang |
| Abstract |
Gene therapy is a very promising technology for treatment of pancreatic ductal adenocarcinoma (PDAC). However, its application has been limited by the abundant stromal response in the tumor microenvironment. The aim of this study was to prepare a dendrimer-based gene-free loading vector with high permeability in the tumor stroma and explore an imaging-guided local gene delivery strategy for PDAC to promote the efficiency of targeted gene delivery. The experimental protocol was approved by the animal ethics committee of Zhongshan Hospital, Fudan University. Third-generation dendrigraft poly-L-lysines was selected as the nanocarrier scaffold, which was modified by cell-penetrating peptides and gadolinium (Gd) chelates. DNA plasmids were loaded with these nanocarriers via electrostatic interaction. The cellular uptake and loaded gene expression were examined in MIA PaCa-2 cell lines in vitro. Permeability of the nanoparticles in the tumor stroma and transfected gene distribution in vivo were studied using a magnetic resonance imaging-guided delivery strategy in an orthotopic nude mouse model of PDAC. The nanocarriers were synthesized with a dendrigraft poly-L-lysine to polyethylene glycol to DTPA ratio of 1:3.4:8.3 and a mean diameter of 110.9±7.7 nm. The luciferases were strictly expressed in the tumor, and the luminescence intensity in mice treated by Gd-DPT/plasmid luciferase (1.04×10(4)±9.75×10(2) p/s/cm(2)/sr) was significantly (P<0.05) higher than in those treated with Gd-DTPA (9.56×10(2)±6.15×10 p/s/cm(2)/sr) and Gd-DP (5.75×10(3)± 7.45×10(2) p/s/cm(2)/sr). Permeability of the nanoparticles modified by cell-penetrating peptides was superior to that of the unmodified counterpart, demonstrating the improved capability of nanoparticles for diffusion in tumor stroma on magnetic resonance imaging. This study demonstrated that an image-guided gene delivery system with a stroma-permeable gene vector could be a potential clinically translatable gene therapy strategy for PDAC. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 2 | 67% |
| Members of the public | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| China | 1 | 3% |
| Unknown | 31 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 28% |
| Student > Ph. D. Student | 6 | 19% |
| Student > Bachelor | 5 | 16% |
| Student > Master | 3 | 9% |
| Student > Doctoral Student | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 4 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 31% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 13% |
| Biochemistry, Genetics and Molecular Biology | 4 | 13% |
| Agricultural and Biological Sciences | 2 | 6% |
| Nursing and Health Professions | 1 | 3% |
| Other | 5 | 16% |
| Unknown | 6 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2015.
All research outputs
#16,048,009
of 25,374,917 outputs
Outputs from International Journal of Nanomedicine
#1,887
of 4,123 outputs
Outputs of similar age
#146,210
of 277,613 outputs
Outputs of similar age from International Journal of Nanomedicine
#53
of 125 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,123 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 277,613 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 125 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.