Abstract
Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.
Highlights
Intramedullary spinal cord tumors (IMSCT) constitute 8 to 10% of primary spinal cord tumors [1] and are uncommon neoplasms characterized by irregular growth of tissue found inside the spinal cord
We show that poly (lactide-co-glycolide) -graft-polyethylenimine (PgP) can efficiently deliver plasmid DNA (pDNA) encoding green fluorescence protein in rat glioblastoma (C6) cells in vitro and deliver pDNA encoding β-galactosidase protein in a rat spinal cord tumor model in vivo
We demonstrated that the cationic amphiphilic copolymer PgP can be a gene carrier due to the stability of polyplexes in the presence of negatively charged serum proteins and the ability to protect pDNA from nucleases in the serum, PgP/pDNA polyplexes maintain bioactivity for transfection after storage at 4 ◦C for up to 4 months—an important feature for commercial and clinical application
Summary
Intramedullary spinal cord tumors (IMSCT) constitute 8 to 10% of primary spinal cord tumors [1] and are uncommon neoplasms characterized by irregular growth of tissue found inside the spinal cord. These tumors cause significant neurologic morbidity and mortality [2], such as pressure on sensitive tissues and reduced function, resulting in pain, sensory changes, and motor deficits. Current treatments for spinal cord tumor include surgical therapy, radiotherapy, and chemotherapy [3,4,5]. Radiation therapy is limited by dose-related toxicity to the normal spinal cord and surrounding tissues, and systemic toxicity [8]. Chemotherapy has been used to treat SCT [9], but it has dose-limiting toxicity and side effects such as sensory neuropathies and gastrointestinal disturbances after systemic administration [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
