ArticleInternational journal of nanomedicine2015
Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer.
Article in International journal of nanomedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 31 citations in OpenAlex.
- Arginine-glycine-aspartate (RGD)-targeted positron-labeled dendritic polylysine nanoprobe for tumor PET imaging.RSC advances · 2020Article
- Dandelion-Like Tailorable Nanoparticles for Tumor Microenvironment Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Pancreatic Cancer: Recent Advances in Nanoformulation-Based Therapies.Critical reviews in therapeutic drug carrier systems · 2019Review
- Sequentially Triggered Nanoparticles with Tumor Penetration and Intelligent Drug Release for Pancreatic Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- Detecting GPC3-Expressing Hepatocellular Carcinoma with L5 Peptide-Guided Pretargeting Approach: In Vitro and In Vivo MR Imaging Experiments.Contrast media & molecular imaging · 2018Article
- Platinum-Based Nanovectors Engineered with Immuno-Modulating Adjuvant for Inhibiting Tumor growth and Promoting Immunity.Theranostics · 2018Article
- Dendrimer- and copolymer-based nanoparticles for magnetic resonance cancer theranostics.Theranostics · 2018Review
- Biological nanoparticles carrying the Hmda-7 gene are effective in inhibiting pancreatic cancer in vitro and in vivo.PloS one · 2017Article
- Article
- Dendritic Polymers for Theranostics.Theranostics · 2016Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGene 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.
methodsThe 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.
resultsThe 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.
conclusionThis 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.
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