Neurotensin-SPDP-poly-l-lysine conjugate: a nonviral vector for targeted gene delivery to neural cells

Martínez‐Fong, Daniel; Navarro-Quiroga, Iván; Ochoa, Ivonne; Álvarez-Maya, Ikuri; Meraz, Marco Antonio; Luna, J.; Arias‐Montaño, José‐Antonio

doi:10.1016/s0169-328x(99)00114-x

Cited by 55 publications

(46 citation statements)

References 48 publications

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“…The NT-polyplex is an attractive alternative because it is specific, effective, biodegradable and nontoxic. 1,3,5,8,12 The new advantage of the NT-polyplex shown in this study is the ability to effectively transfect tumoral cells after its administration through the blood stream. This feature will be of great use to target metastasis sites very small or unreachable by surgery.…”

Section: Discussionmentioning

confidence: 92%

“…These results support that the systemic transfection of the NT-polyplex depends on NTSR1, as shown previously using blockage assays with either NT (1 mM) or SR 48692, a synthetic NT competitive antagonist. 1,3,5,8 The specificity was also demonstrated by the negative results of internalization and expression assays after the systemic transfection with an untargeted polyplex (without the ligand NT) or the KP-pDNA complex. The second conclusion is that the specific transfection of a suicide gene into neuroblastoma tumor cells expressing NTSR1 causes a therapeutic effect.…”

Section: Discussionmentioning

confidence: 98%

“…1,2 This nonviral system consists of poly-L-lysine, NT, a fusogenic peptide (FP), a karyophilic peptide (KP) and a plasmid encompassing the coding sequence for a protein of interest (transgene). The components of the NT-polyplex allow the transgene to enter the cells, carry the transgene toward the cytosol and reach the cell nucleus.…”

Section: Introductionmentioning

confidence: 99%

“…The NTpolyplex could be a specific tool to transfer therapeutic genes to neuroblastoma tumors because several human cell lines express NTSR1. 16,17 In this work, the murine neuroblastoma N1E-115 cell line, which has been efficiently transfected by NT-polyplex in culture 1,2,8 because they overexpressed the NTSR1, 18 was allografted in athymic mice to develop an animal model of a neuroblastoma tumor. We hypothesized that the NTpolyplex will be able to transfer genes into neuroblastoma tumor cells after its injection into the tumor or through the blood stream.…”

Section: Introductionmentioning

confidence: 99%

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NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

et al. 2009

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and 4 Molecular and Steroid hormones, Neurotensin and Tumor Progression INSERM UPMC Cdr Saint-Antoine Eq 7, Paris, France Neurotensin (NT)-polyplex is a nonviral system for the targeted gene delivery to cells that express and internalize the high-affinity NT receptor (NTSR1). In hemiparkinsonian rats, we previously demonstrated the morphological and functional recovery from dopaminergic neurodegeneration using the NT-polyplex as a vehicle to transfect a neurotrophic gene. The main objective of this work was to demonstrate the feasibility of NT-polyplex to transfect reporter or therapeutic genes into neuroblastoma tumors through the blood stream or by intratumoral injection. N1E-115 cells known to express NTSR1 were allografted into athymic mice to generate the neuroblastoma tumor model. Both routes of administration allowed the NT-polyplex to reach and transfect tumoral cells. A low transgene expression was also detected in intestinal tract cells only after the injection into the blood stream. The transfection of the thymidine kinase (HSVTK) suicide gene followed by ganciclovir (GCV) treatment decreased the size and weight of neuroblastoma tumors by 30-50% and increased apoptosis compared to controls. This study shows the potential of the NTpolyplex as specific gene-transfer system for NTSR1 cancer cells.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

et al. 2009

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“…A few polymeric vectors have been investigated as a potential alternative to viral vectors. As an approach for effective polymeric gene transfection, polymeric vectors have been designed to target specific receptors expressed on secretory cells (i.e., sulfonylurea receptors (SUR) on insulinsecreting cells (7), high-affinity neurotensin receptors on neuronal cells (8), and nerve growth factor receptors on dopamine-secreting cells (9)). …”

Section: Introductionmentioning

confidence: 99%