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Your search keyword '"McCaffrey, Joanne"' showing total 3 results
Start Over Author "McCaffrey, Joanne" Topic amphipathic peptide
3 results on '"McCaffrey, Joanne"'

2. Systemic RALA/iNOS nanoparticles; a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment

Author

McCrudden, Cian M., McBride, John W., McCaffrey, Joanne, Ali, Ahlam A., Dunne, Nicholas J., Kett, Vicky L., Coulter, Jonathan A., Robson, Tracy, and McCarthy, Helen O.

Subjects
Prostate cancer, Radiation, Nitric oxide synthase, nanoparticle, Carcinoma, lcsh:RM1-950, Promoter, Tumor cells, breast cancer, lcsh:Therapeutics. Pharmacology, SDG 3 - Good Health and Well-being, Mesenchymal transition, nitric oxide, nonviral gene therapy, metastasis, Original Article, Amphipathic peptide, Human osteocalcin, Delivery
Abstract

This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [CMV]-driven or transcriptionally regulated human osteocalcin [hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-luc-D3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. Keywords: nonviral gene therapy, nitric oxide, nanoparticle, breast cancer, metastasis

Published
2017
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3. Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery.

Author

McCarthy, Helen O., McCaffrey, Joanne, McCrudden, Cian M., Zholobenko, Aleksey, Ali, Ahlam A., McBride, John W., Massey, Ashley S., Pentlavalli, Sreekanth, Chen, Kun-Hung, Cole, Grace, Loughran, Stephen P., Dunne, Nicholas J., Donnelly, Ryan F., Kett, Victoria L., and Robson, Tracy

Subjects
*DRUG development, *MOLECULAR self-assembly, *NANOMEDICINE, *AMPHIPHILES, *PEPTIDE analysis, *GENE delivery techniques, *DRUG design, *GENE therapy
Abstract

The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were < 100 nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics. [ABSTRACT FROM AUTHOR]

Published
2014
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