Targeted delivery of irinotecan and SLP2 shRNA with GRP-conjugated magnetic graphene oxide for glioblastoma treatment.
Chi-Cheng ChuangYu-Hsiang LanYu-Jen LuYu-Lun WengJyh-Ping ChenPublished in: Biomaterials science (2022)
Magnetic nanoparticles (MNPs) are useful for magnetic targeted drug delivery while ligand-mediated active targeting is another common delivery strategy for cancer therapy. In this work, we intend to prepare magnetic graphene oxide (mGO) by chemical co-precipitation of MNPs on the GO surface, followed by conjugation of the gastrin releasing peptide (GRP) as a targeting ligand, for dual targeted drug/gene delivery in invasive brain glioma treatment. mGO was grafted with chitosan, complexed with shRNA plasmid DNA for stomatin-like protein 2 (SLP2) gene silencing, modified with urocanic acid for plasmid DNA endosomal escape, PEGylated for GRP conjugation, and loaded with the chemotherapeutic drug irinotecan (CPT-11) by π-π interaction for pH-responsive drug release (mGOCUG/CPT-11/shRNA). In addition to the in depth characterization of the physico-chemical and biological properties during each preparation step, we also study the loading/pH-responsive release behavior of CPT-11 and the shRNA plasmid loading/cell transfection efficiency. The targeting and antitumor efficacies of the nanocomposite were studied with U87 human glioblastoma cells in vitro . An in vivo study revealed that intravenous administration followed by magnetic guidance results in the efficient targeted delivery of mGOCUG/CPT-11/shRNA to orthotopic brain tumors in nude mice, and it exhibits excellent antitumor efficacy with a reduced tumor growth rate and prolonged animal survival time. Our work thus highlights a multifunctional mGO-based drug/gene delivery platform for effective combination cancer therapy in glioblastoma treatment.
Keyphrases
- cancer therapy
- drug delivery
- drug release
- escherichia coli
- molecularly imprinted
- endoplasmic reticulum stress
- stem cells
- crispr cas
- type diabetes
- endothelial cells
- induced apoptosis
- optical coherence tomography
- magnetic nanoparticles
- multiple sclerosis
- bone marrow
- single cell
- white matter
- circulating tumor
- signaling pathway
- photodynamic therapy
- insulin resistance
- cell proliferation
- oxidative stress
- mass spectrometry
- high dose
- brain injury
- highly efficient
- skeletal muscle
- functional connectivity
- cell death