A serum-resistant polyamidoamine-based polypeptide dendrimer for gene transfection

Wang, Hongmei; Pan, Shaowei; Chen, M.W.; Wu, Y.; Wang, C.; Wen, Yuting; Zeng, Xiaofeng; Wu, Chao

doi:10.1016/j.biomaterials.2010.09.045

Cited by 58 publications

(45 citation statements)

References 26 publications

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“…Examples of nonviral vectors include bacteria [5], cell-penetrating peptides [6], functionalized gold nanoparticles (NPs) or carbon nanotubes [7-10], and cationic polymers. Among these nonviral vectors, cationic polymers including polyethyleneimine (PEI) [11], poly(l-lysine) (PLL) [11, 12], chitosan [13], dendrimers [14, 15] and cationic lipids [16] have the advantages of being scalable for manufacturing in quantity, having low immunogenicity, the capacity for selective chemical modification and the ability to carry large inserts. Due to its superior transfection efficiency in a broad range of cell types, synthetic PEI has a privileged place among nonviral gene delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Dual-purpose magnetic micelles for MRI and gene delivery

Wang

Sheshala

Martinez

et al. 2012

Journal of Controlled Release

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Gene therapy is a promising therapeutic approach for treating disease, but the efficient delivery of genes to desired locations with minimal side effects remains a challenge. In addition to gene therapy, it is also highly desirable to provide sensitive imaging information in patients for disease diagnosis, screening and post-therapy monitoring. Here, we report on the development of dual-purpose chitosan and polyethyleneimine (PEI) coated magnetic micelles (CP-mag-micelles) that can deliver nucleic acid-based therapeutic agents and also provide magnetic resonance imaging (MRI). These ‘theranostic’ CP-mag-micelles are composed of monodisperse hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) loaded into the cores of micelles that are self-assembled from a block copolymer of poly (D, L-lactide) (PLA) and monomethoxy polyethylene glycol (mPEG). For efficient loading and protection of the nucleic acids the micelles were coated with cationic polymers, such as chitosan and PEI. The morphology and size distribution of the CP-mag-micelles were characterized and their potential for use as an MRI-probe was tested using an MRI scanner. The T2 relaxivity of micelles was similar to CP-mag-micelles confirming that coating with cationic polymers did not alter magnetism. Nanoparticles coated with chitosan:PEI at a weight ratio of 5:5 showed higher transfection efficiency in HEK293, 3T3 and PC3 cells than with weight ratios of 3:7 or 7:3. CP-mag-micelles are biocompatible, can be delivered to various organs and are safe. A single injection of CP-mag-micelles carrying reporter plasmids in vivo expressed genes for at least one week. Collectively, our results demonstrate that a structural reinforcement of SPIONs loaded in the core of an mPEG-PLA micelle coated with cationic polymers provides efficient DNA delivery and enhanced MRI potential, and affords a promising candidate for theranostics in the future.

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Section: Introductionmentioning

confidence: 99%

Dual-purpose magnetic micelles for MRI and gene delivery

Wang

Sheshala

Martinez

et al. 2012

Journal of Controlled Release

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“…This class of biopolymers is also concerned by the previously mentioned general trends. Some successful attempts undertaken to design new dendritic polypeptide-like molecules as well as other water soluble dendrimers (for instance well-known poly(amido amine) (PAMAM)) had demonstrated the benefits of turning the shape and surface properties of such structurally ordered macromolecules [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Hydrodynamic Behavior of Dendrigraft Polylysines in Water and Dimethylformamide

et al. 2012

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Abstract:The four first generations of dendrigraft poly-L-lysine have been studied in dimethylformamide (aprotic solvent) and in 0.2 M NaCl aqueous solutions by isothermal translation diffusion, 1 H NMR and viscometry methods. The relationships between diffusion coefficient, intrinsic viscosity and molar mass have been determined for dendrigraft poly-L-lysines, and the scaling index values have been compared to classical trifunctional dendrimers. Dendrimers and dendrigraft poly-L-lysines exhibited similitudes in their hydrodynamic behaviors. Nevertheless, dendrigraft poly-L-lysines displayed a specific behavior in solution. In contrast to dendrimers, a significant change of hydrodynamic dimension of dendrigraft poly-L-lysines according to the nature of the solvent has been observed. In aprotic solvent, the dendrigraft poly-L-lysine dimensions are about two times lower than in aqueous media (i.e., the hydrodynamic volume is contracted by a factor 8 in dimethylformamide), revealing the softness of dendrigraft poly-L-lysine compared to classical trifunctional dendrimers. OPEN ACCESSPolymers 2012, 4 21

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“…In order to overcome one or several of the barriers to nonviral transfection to improve gene transfer efficiency, most previous work has focused on physicochemical modifications of the complexing agent [11-14]. Other work has moved beyond the scope of physicochemical vector modifications and placed a focus on the extracellular microenvironment and its role in nonviral gene transfer [15-17], demonstrating that extracellular characteristics such as substrate stiffness, the presence of extracellular matrix (ECM) proteins, and RGD cell adhesion ligand density modulate nonviral gene transfer [18,19].…”

Section: Introductionmentioning

confidence: 99%

The role of surface chemistry-induced cell characteristics on nonviral gene delivery to mouse fibroblasts

Kasputis

Pannier

2012

J Biol Eng

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BackgroundGene delivery approaches serve as a platform to modify gene expression of a cell population with applications including functional genomics, tissue engineering, and gene therapy. The delivery of exogenous genetic material via nonviral vectors has proven to be less toxic and to cause less of an immune response in comparison to viral vectors, but with decreased efficiency of gene transfer. Attempts have been made to improve nonviral gene transfer efficiency by modifying physicochemical properties of gene delivery vectors as well as developing new delivery techniques. In order to further improve and understand nonviral gene delivery, our approach focuses on the cell-material interface, since materials are known to modulate cell behavior, potentially rendering cells more responsive to nonviral gene transfer. In this study, self-assembled monolayers of alkanethiols on gold were employed as model biomaterial interfaces with varying surface chemistries. NIH/3T3 mouse fibroblasts were seeded on the modified surfaces and transfected using either lipid- or polymer- based complexing agents.ResultsTransfection was increased in cells on charged hydrophilic surfaces presenting carboxylic acid terminal functional groups, while cells on uncharged hydrophobic surfaces presenting methyl terminations demonstrated reduced transfection for both complexing agents. Surface–induced cellular characteristics that were hypothesized to affect nonviral gene transfer were subsequently investigated. Cells on charged hydrophilic surfaces presented higher cell densities, more cell spreading, more cells with ellipsoid morphologies, and increased quantities of focal adhesions and cytoskeleton features within cells, in contrast to cell on uncharged hydrophobic surfaces, and these cell behaviors were subsequently correlated to transfection characteristics.ConclusionsExtracellular influences on nonviral gene delivery were investigated by evaluating the upregulation and downregulation of transgene expression as a function of the cell behaviors induced by changes in the cells’ microenvronments. This study demonstrates that simple surface modifications can lead to changes in the efficiency of nonviral gene delivery. In addition, statistically significant differences in various surface-induced cell characteristics were statistically correlated to transfection trends in fibroblasts using both lipid and polymer mediated DNA delivery approaches. The correlations between the evaluated complexing agents and cell behaviors (cell density, spreading, shape, cytoskeleton, focal adhesions, and viability) suggest that polymer-mediated transfection is correlated to cell morphological traits while lipid-mediated transfection correlates to proliferative characteristics.

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A serum-resistant polyamidoamine-based polypeptide dendrimer for gene transfection

Cited by 58 publications

References 26 publications

Dual-purpose magnetic micelles for MRI and gene delivery

Dual-purpose magnetic micelles for MRI and gene delivery

Hydrodynamic Behavior of Dendrigraft Polylysines in Water and Dimethylformamide

The role of surface chemistry-induced cell characteristics on nonviral gene delivery to mouse fibroblasts

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