Cyclam-Based Polymeric Copper Chelators for Gene Delivery and Potential PET Imaging

Li, Jing; Zhu, Yu; Hazeldine, Stuart; Firestine, Steven M.; Oupický, David

doi:10.1021/bm3009999

Cited by 21 publications

(12 citation statements)

References 41 publications

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“…Plerixafor functions as a hexafunctional monomer in the Michael polyaddition and its use leads to either insoluble crosslinked PAMD or soluble branched PAMD if the reaction is performed at low temperatures and low monomer concentrations (32, 33). Optimizing the reaction conditions allowed us to synthesize soluble PAMD with weight-average molecular weight of 10.6 kDa and unimodal distribution of molecular weights (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Wang

Oupický

2014

Pharm Res

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Purpose To determine the effect of PEG modification on pharmacologic and gene delivery properties of polymeric CXCR4 antagonist based on Plerixafor. Methods Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized polymers was determined using receptor redistribution assay. Inhibition of cancer cell invasion by the polyplexes of the synthesized polymers was assessed using Boyden-chamber method. Transfection activity of DNA polyplexes formed with the synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma cells. Results Our results demonstrate that modification of PAMD with PEG decreased toxicity of the polymers, while preserving their CXCR4 antagonism. Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on transfection activity of PEG-PAMD polyplexes could be overcome by using polyplexes formulated with a mixture of PAMD and PEG-PAMD. Conclusion Modification of PAMD with PEG is a viable strategy to preserve the desirable CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while improving safety and colloidal stability of the PAMD polyplexes.

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Section: Resultsmentioning

confidence: 99%

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Wang

Oupický

2014

Pharm Res

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“…[58] The versatility of Michael polyaddition was recently demonstrated even on monomers such as cyclam (12) and bicyclam CXCR4 antagonist Plerixafor (13) containing multiple secondary amines. [59,60]…”

Section: Poly(amido Amine)smentioning

confidence: 99%

Bioreducible Polycations in Nucleic Acid Delivery: Past, Present, and Future Trends

Oupický

2014

Macromolecular Bioscience

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Polycations that are degradable by reduction of disulfide bonds are developed for applications in delivery of nucleic acids. This paper surveys methods of synthesis of bioreducible polycations and discusses current understanding of the mechanism of action of bioreducible polyplexes. Emphasis is placed on the relationship between the biological redox environment and toxicity, trafficking, transfection activity, and in vivo behavior of bioreducible polycations and polyplexes.

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“…We carried out gel electrophoresis of 2X3, 2S3, and 2S4 lipoplexes with pDNA in the presence of GSH and/or heparin (Figure ). Heparin is often used along with GSH or DTT to study lipoplex stability . Results demonstrated than incubation of the lipoplexes with GSH did not induce pDNA release.…”

Section: Resultsmentioning

confidence: 99%

Position of Disulfide Bond Determines the Properties of Novel Stimuli‐Responsive Cationic Lipids

et al. 2020

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Effective release of nucleic acids from the lipoplexes to the cytoplasm is one of the challenges of gene delivery systems. Stimuli-responsive groups such as disulfide linkages offer an attractive solution. We designed two novel polycationic amphiphiles with disulfide links (2S3 and 2S4) and compared their transfection efficiency with their nonredox-sensitive analogue 2X3. The stability and redox sensitivity of lipoplexes formed by cationic liposomes 2X3, 2S3, and 2S4 with plasmid DNA were studied using different destabilizing agents, such as glutathione, 1,4-dithiothreitol, and heparin using electrophoresis and fluorescent titration assays. Further, we performed size and ζ-potential analysis of cationic liposomes and lipoplexes, and also compared their transfection efficiencies in the presence of the destabilizing agents. Depending on their structure, disulfide lipoplexes exhibited different sensitivity towards the destabilizing agents. Moreover, high redoxsensitivity correlated well with higher transfection activity into HEK293 cells.

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Cyclam-Based Polymeric Copper Chelators for Gene Delivery and Potential PET Imaging

Cited by 21 publications

References 41 publications

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Bioreducible Polycations in Nucleic Acid Delivery: Past, Present, and Future Trends

Position of Disulfide Bond Determines the Properties of Novel Stimuli‐Responsive Cationic Lipids

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