A dimethylmaleic acid–melittin‐polylysine conjugate with reduced toxicity, pH‐triggered endosomolytic activity and enhanced gene transfer potential

Meyer, Martin; Zintchenko, Arkadi; Ogris, Manfred; Wagner, Ernst

doi:10.1002/jgm.1075

Cited by 82 publications

(69 citation statements)

References 35 publications

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“…Their sizes could not be measured at pH 5.5 and 6.0 (Figure 4a) due to aggregation. This was a result of the weakened solubility of N -nap- O -MalCS in the aqueous phase caused by acid hydrolysis of its maleoyl groups [80,81]. This phenomenon accelerated at 37°C compared to 25°C (Figure 4b).…”

Section: Resultsmentioning

confidence: 99%

Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

et al. 2013

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Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

et al. 2013

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“…7). [174,175] Endosomolysis can not only be achieved with toxins known from nature: some synthetic vectors display this feature as well. For example bPEI is not only used for the complexation of nucleotides, it is also known to have some inherent endosomolytic ability.…”

Section: Disulfides For the Attachment Of Endosomolytic Agentsmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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Nucleic acids are not only expected to assume a pivotal position as "drugs" in the treatment of genetic and acquired diseases, but could also act as molecular cues to control the microenvironment during tissue regeneration. Despite this promise, the efficient delivery of nucleic acids to their side of action is still the major hurdle. One among many prerequisites for a successful carrier system for nucleic acids is high stability in the extracellular environment, accompanied by an efficient release of the cargo in the intracellular compartment. A promising strategy to create such an interactive delivery system is to exploit the redox gradient between the extra- and intracellular compartments. In this review, emphasis is placed on the biological rationale for the synthesis of redox sensitive, disulfide-based carrier systems, as well as the extra- and intracellular processing of macromolecules containing disulfide bonds. Moreover, the basic synthetic approaches for introducing disulfide bonds into carrier molecules, together with examples that demonstrate the benefit of disulfides at the individual stages of nucleic acid delivery, will be presented.

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“…The simplest strategy to improve the transfection efficiency of PLys polyplexes is to provide them with endosome-escaping functions, avoiding lysosomal degradation of loading pDNA. Several previous studies have reported about the integration of endosome-escaping elements into PLys polyplexes, including membrane-fusion peptides [11,12] and buffering units with low pKa, such as histidine. [13,14] [15,16] .…”

Section: Introductionmentioning

confidence: 99%

pDNA/poly(L‐lysine) Polyplexes Functionalized with a pH‐Sensitive Charge‐Conversional Poly(aspartamide) Derivative for Controlled Gene Delivery to Human Umbilical Vein Endothelial Cells

Sanjoh

Hiki

Lee

et al. 2010

Macromol. Rapid Commun.

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An efficient endosome-escaping function was integrated into the polyplex of plasmid DNA (pDNA) with poly(L-lysine) (PLys) to improve its gene transfection efficiency through electrostatic coating with charge-conversional polymer (CCP). CCP showed charge-conversional function responding to endosomal pH, leading to the release of pDNA/PLys polyplex into the cytoplasm. The cells took up the intact CCP-integrated ternary polyplex, which exerted appreciably higher transfection efficiency with lower cytotoxicity than pDNA/PLys polyplex against human umbilical vein endothelial cells (HUVECs). This is consistent with the facilitated endosomal escape of the CCP-integrated ternary polyplex compared to the pDNA/PLys polyplex as directly observed with confocal laser-scanning microscopy.

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A dimethylmaleic acid–melittin‐polylysine conjugate with reduced toxicity, pH‐triggered endosomolytic activity and enhanced gene transfer potential

Abstract: Modification of the polycationic carrier PLL with DMMAn-masked melittin not only enhances gene transfer efficiency, but also strongly reduces the acute toxicity of melittin and PLL. Hence this modification might be useful for optimizing polycationic gene carriers.

Cited by 82 publications

References 35 publications

Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

pDNA/poly(L‐lysine) Polyplexes Functionalized with a pH‐Sensitive Charge‐Conversional Poly(aspartamide) Derivative for Controlled Gene Delivery to Human Umbilical Vein Endothelial Cells

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