title: Generation of a focused poly(amino ether) library: polymer-mediated transgene delivery and gold-nanorod based theranostic systems.
abstract: A focused library of twenty-one cationic poly(amino ethers) was synthesized following ring-opening polymerization of two diglycidyl ethers by different oligoamines. The polymers were screened in parallel for plasmid DNA (pDNA) delivery, and transgene expression efficacies of individual polymers were compared to those of 25 kDa polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression than PEI in pancreatic and prostate cancer cells lines were identified from the screen. All seven lead polymers showed highest transgene expression at a polymer:pDNA weight ratio of 5:1 in the MIA PaCa-2 pancreatic cancer cell line. Among the conditions studied, transgene expression efficacy correlated with minimal polymer cytotoxicity but not polyplex sizes. In addition, this study indicated that methylene spacing between amine centers in the monomers, amine content, and molecular weight of the polymers are all significant factors and should be considered when designing polymers for transgene delivery. A lead effective polymer was employed for coating gold nanorods, leading to theranostic nanoassemblies that possess combined transgene delivery and optical imaging capabilities, leading to potential theranostic systems.
authors: Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA.
authors: Lucas
authors: L
authors: Vu
authors: James
authors: J
authors: Ramos
authors: Thrimoorthy
authors: T
authors: Potta
authors: Kaushal
authors: K
authors: Rege
mesh_terms: D000588:Amines / Q000737:chemistry; D016923:Cell Death; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004986:Ether / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006046:Gold / Q000737:chemistry*; D006801:Humans; D057446:Hydrodynamics; D008156:Luciferases / Q000378:metabolism; D008970:Molecular Weight; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D019076:Transgenes / Q000235:genetics*
chemical_list: D000588:Amines; D011073:Polyamines; D004986:Ether; D006046:Gold; D008156:Luciferases
keywords: combinatorial synthesis; gold nanorods; non viral gene delivery; polymer library.; two photon imaging
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