Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study

Griffiths, Peter Charles; Nilmini, Renuka; Carter, Emma; Dodds, Patrick S.; Murphy, D. M.; Khayat, Zeena; Lattanzio, Ettore; Ferruti, Paolo; Heenan, Richard K.; King, Stephen M.; Duncan, Ruth

doi:10.1002/mabi.201000040

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…The results of the above papers on PAAs as protein carriers are in agreement with the previously mentioned results of basic research in the same field and, not unexpectedly, point to a similar conclusion. By a proper design of the acid/base properties and the hydrophobic/hydrophilic balance, there is little doubt that a number of PAAs may display intracellular protein transport ability.…”

Section: Biomedical and Biotechnological Applications Of Paassupporting

confidence: 89%

“…47) analogue was used to give a measure of the polymer flexibility. No interaction was found adding ISA23 to the external vesicle surface . This observation conflicts with the reported ability of ISA23 to lyse the membrane of red blood cells (RBC) at pH ≤ 5, but is in agreement with previous studies showing no effect on membrane permeability when this PAA was added to an incubation medium containing isolated lysosomal vesicles, whereas destabilized the lysosomal membrane if internalized into the lysosomal compartment .…”

Section: Biomedical and Biotechnological Applications Of Paassupporting

confidence: 71%

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Poly(amidoamine)s: Past, present, and perspectives

Ferruti

2013

J. Polym. Sci. Part A: Polym. Chem.

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122

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Poly(amidoamine)s (PAAs) are a family of synthetic polymers obtained by stepwise polyaddition of prim-or sec-amines to bisacrylamides. Nearly all conceivable bisacrylamides and prim-or sec-amines can be employed as monomers endowing PAAs of a structural versatility nearly unique among stepwise polyaddition polymers. PAAs are degradable in aqueous media, including physiological fluids. Many of them are remarkably biocompatible notwithstanding their cationic character. PAAs are per se highly functional polymers and, in addition, can be further functionalized giving rise to an endless variety of polymeric structures meeting the requisites for applications in such apparently disparate fields as inorganic water pollutants scavengers, sensors, drug and protein intracellular carriers, transfection promoters, peptidomimetic antiviral and antimalarial agents. In this review, the unique chemistry of PAAs is discussed and a vast library of PAA structures and PAA applications from the beginning to the present days reported.

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Section: Biomedical and Biotechnological Applications Of Paassupporting

confidence: 89%

Section: Biomedical and Biotechnological Applications Of Paassupporting

confidence: 71%

Poly(amidoamine)s: Past, present, and perspectives

Ferruti

2013

J. Polym. Sci. Part A: Polym. Chem.

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122

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“…It has been shown that, during endocytosis and endosomal maturation, there is a gradual change in the pH from 6.0–6.2 in early endosome to 5.5 in late endosome to 4.5–5 in lysosome . Thus, developing polymeric systems that can rapidly degrade in a controlled way could possibly disrupt the endosome due to osmotic imbalance and help endosomal escape and cytosolic delivery of therapeutic agents. − Thus, we investigated the degradation of pPKHE polymers in cells using fluorescent derivatives. The cellular uptake and subsequent trafficking of fluorescent-labeled polymers were examined using confocal microscopy at various time intervals.…”

Section: Resultsmentioning

confidence: 99%

Branched Multifunctional Polyether Polyketals: Variation of Ketal Group Structure Enables Unprecedented Control over Polymer Degradation in Solution and within Cells

et al. 2012

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Multifunctional biocompatible and biodegradable nanomaterials incorporating specific degradable linkages that respond to various stimuli and with defined degradation profiles are critical to the advancement of targeted nanomedicine. Herein we report, for the first time, a new class of multifunctional dendritic polyether polyketals containing different ketal linkages in their backbone that exhibit unprecedented control over degradation in solution and within the cells. High-molecular-weight and highly compact poly(ketal hydroxyethers) (PKHEs) were synthesized from newly designed α-epoxy-ω-hydroxyl-functionalized AB(2)-type ketal monomers carrying structurally different ketal groups (both cyclic and acyclic) with good control over polymer properties by anionic ring-opening multibranching polymerization. Polymer functionalization with multiple azide and amine groups was achieved without degradation of the ketal group. The polymer degradation was controlled primarily by the differences in the structure and torsional strain of the substituted ketal groups in the main chain, while for polymers with linear (acyclic) ketal groups, the hydrophobicity of the polymer may play an additional role. This was supported by the log P values of the monomers and the hydrophobicity of the polymers determined by fluorescence spectroscopy using pyrene as the probe. A range of hydrolysis half-lives of the polymers at mild acidic pH values was achieved, from a few minutes to a few hundred days, directly correlating with the differences in ketal group structures. Confocal microscopy analyses demonstrated similar degradation profiles for PKHEs within live cells, as seen in solution and the delivery of fluorescent marker to the cytosol. The cell viability measured by MTS assay and blood compatibility determined by complement activation, platelet activation, and coagulation assays demonstrate that PKHEs and their degradation products are highly biocompatible. Taken together, these data demonstrate the utility this new class of biodegradable polymer as a highly promising candidate in the development of multifunctional nanomedicine.

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“…But at pH 7.4, the deprotonated carboxyl group hindered the interaction between the polymer and anionic membrane. This was partly due to the polymer's tightly coiled conformation and more significantly, due to the repulsion like negative charges at polymer/membrane interface . As a result, ISA23 was nonhemolytic, and when injected, exhibited “stealthlike” properties and circulated for a long time in the blood stream without being recognized by the liver.…”

Section: Effects Of Various Functional Groups On Properties Of Poly(amentioning

confidence: 99%

Structure–Function Correlations of Poly(Amido Amine)s for Gene Delivery

Sun

Xian

et al. 2016

Macromolecular Bioscience

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Poly(amido amine)s' (PAAs) versatility are nearly unique among stepwise polymers. Different functional groups can be easily introduced into these polymers to add functionality such as cell internalization, charge-shift, bioreducibility, "stealth" properties, and targeting moieties, while maintaining the bulk structural integrity of these polymers. The poly(amido amine)s are used as a unique research platform to elucidate their complex structure-function relationship. It is shown that guanidinium group, carboxyl group, disulfide bond, alkyl chain, branching, acetyl groups, benzoyl groups, and quaternary nicotinamide moieties can influence many steps of gene delivery, such as DNA condensation, cellular uptake, endosomal escape, nuclear entry, and finally gene expression. The authors systematically discuss the structure-function correlations of PAAs for gene delivery, and elaborate how the properties of polymers can be adjusted by changing the polymeric structure.

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Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study

Cited by 6 publications

References 38 publications

Poly(amidoamine)s: Past, present, and perspectives

Poly(amidoamine)s: Past, present, and perspectives

Branched Multifunctional Polyether Polyketals: Variation of Ketal Group Structure Enables Unprecedented Control over Polymer Degradation in Solution and within Cells

Structure–Function Correlations of Poly(Amido Amine)s for Gene Delivery

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