title: Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles.
abstract: Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100-180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers.
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O.Box 71345-1583, Shiraz, Iran. dehshahria@sums.ac.ir.|Pharmaceutical Sciences Research Center, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. dehshahria@sums.ac.ir.|Center for Nanotechnology in Drug Delivery, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. dehshahria@sums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Dehshahri
authors.affiliation: Department of Medicinal Chemistry, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Sadeghpour
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O.Box 71345-1583, Shiraz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Keykhaee
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O.Box 71345-1583, Shiraz, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Khalvati
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O.Box 71345-1583, Shiraz, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sheikhsaran
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010316:Particle Size; D004369:Pentetic Acid / Q000737:chemistry / Q000627:therapeutic use; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D018664:Interleukin-12; D004369:Pentetic Acid; D011094:Polyethyleneimine
keywords: Cytotoxicity; Gene delivery; Interleukin-12; Nanoparticle; Polyethylenimine