Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity

Nam, Hye Yeong; Nam, Ki Woong; Hahn, Hwa Jeong; Kim, Bo Hye; Lim, Hyun Jung; Kim, Hyun Jin; Choi, Joon Sig; Park, Jong‐Sang

doi:10.1016/j.biomaterials.2008.10.013

Cited by 143 publications

(87 citation statements)

References 27 publications

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“…A different approach to reduce cytotoxicity in polycationic vectors was to introduce hydrolyzable linkages, as the ester groups, as applied both to PAMAM 30 itself and to non dendrimeric vectors such as poly(β-amino esters). [31][32][33] Moreover, dendrimers containing amino acid residues 26,[34][35][36] have aroused great interest since the diversity of amino acid moiety can meet the recognized requirement for modulating the buffer capacity of the vector and facilitate its escape from endosomal acidic compartments through membrane disruption of endosomes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

Alfei¹,

Castellaro²,

Taptue³

2017

Org. Commun.

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Dendrimers, the emerging man made, highly branched, star-shaped macromolecules with nanometerscale dimensions are well known for their well defined and high controlled architecture, their versatility and high functionality and are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper, versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. A fourth generation dendrimer equipped with 48 peripheral hydroxyl groups was prepared from 2,2-bis(hydroxymethyl)propanoic acid and was used for grafting BOC-amino acids or as "hypercores" on which dendrons functionalized with BOC-amino acids were attached. A library of 15 polycationic homo-and hetero-dendrimers in the form of hydrochloride was obtained. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration. Their buffer capacity and results obtained from cytotoxicity assays and tests of binding with both pDNA and siRNA were very satisfactory. Keywords:Polyester-based polycationic dendrimers; 2, 2-bis(hydroxymethyl)propanoic acid; amino acids; pDNA and siRNA binding; buffer capacity.

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Section: Introductionmentioning

confidence: 99%

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

Alfei¹,

Castellaro²,

Taptue³

2017

Org. Commun.

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“…A great deal of research has been done on introducing arginine into polymers such as PAMAM dendrimers to improve their transfection efficiency [14,51]. The interesting studies of Nam et al further confirmed that PAMAM dendrimers (G3 and G4) conjugated with arginine (PAMAM-R) or lysine (PAMAM-K) through an amide bound have been found to have better transfection properties compared to plain G3 and G4 [52,53]. Moreover, the authors noticed that the attachment of arginine to PAMAM dendrimers through a biodegradable ester bond has at least two advantages.…”

mentioning

confidence: 63%

“…These newly synthesized biodegradable e-PAM-R and e-PAM-K dendrimers, which have a degradable ester bond in the arginine-and lysine-grafted PAMAM dendrimers, show the capability for reducing overall toxicity through blocking the accumulation of more toxic cationic polymers. Therefore, it is expected that PAMAM-OH dendrimers (specially those surfacemodified with arginine) will have excellent potential to be a safe gene delivery carrier possessing biodegradability, low cytotoxicity, and high transfection efficiency [53]. In a study performed by Pisal et al, the permeability across Caco-2 cell monolayers, and cytotoxicity of PAMAM G4 dendrimers conjugated with arginine and ornithine, was investigated [54].…”

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confidence: 99%

PAMAM dendrimers — diverse biomedical applications. Facts and unresolved questions

Łabieniec

Watała

2009

Open Life Sciences

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Abstract:In this mini-review a number of novel outcomes, originating from studies in the field of PAMAM dendrimers, are presented and discussed. Owing to the multi-disciplinary nature of dendrimer chemistry it seems important to focus on the relevant topical research of PAMAM dendrimers, including their function, toxicity, surface modifications, and also possible new applications of these spherical polymers. We also consider the possibilities of specific functionalisation of PAMAM dendrimers -both novel ideas and those that have already been reported; as well as their cell-mediated effects (toxic and non-toxic). Then the reactivity of dendrimers' terminal groups, and their anticipated protective role against modifications of biomacromolecules, are discussed with regard to future developments in biomedical research. Mini-Review AbbreviationsAGEs -advanced glycation end products; AOPP -advanced oxidation protein products; RCI (S 3 *S 4 -1 ) -respiration control index (how mitochondria respond to ADP with enhanced oxygen consumption); ADP:O -coefficient of oxidative phosphorylation (how is respiration linked to phosphorylation); IC 50 -the concentration for which the 50% inhibition occurs; OPR -oxidative phosphorylation rate (how fast is ATP generated), MTT assay -standard colorimetric cytotoxicity test with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide as a substrate; PAMAM -poly(amido)amine dendrimers; PEI -polyethyleneimine; S 3 -rate of oxygen uptake by mitochondria stimulated with ADP -state 3 (how fast is oxygen consumed by mitochondria in the presence of ADP and substrate); S 4 -rate of basal oxygen uptake by mitochondria -state 4 (how fast is oxygen consumed by mitochondria in the presence of substrate and the absence of ADP).

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“…31 Aptamer was coupled to the remote end of the PEG chain, triggering the receptormediated mechanism to increase the accumulation of DNA/ PAMAM-PEG-APT in prostate cancer. The sizes and zeta potentials of the pEGFP/PAMAM-PEG-APT complexes were analyzed using the Zetasizer Nano-ZS90 over a range of N/P ratios.…”

Section: Results and Discussion Characterization Of Pamam Derivativesmentioning

confidence: 99%

Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy

Ding²,

Gao³

et al. 2011

IJN

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Background: miR-15a and miR-16-1 have been identified as tumor suppressor genes in prostate cancer, but their safe and effective delivery to target cells is key to the successful use of this therapeutic strategy. RNA aptamer A10 has been used as a ligand, targeting prostate cancer cells that express prostate-specific membrane antigen (PSMA). Compared with A10, the binding of the second-generation RNA aptamer, A10-3.2, to PSMA is more efficient. Methods: A10-3.2 was investigated as a PSMA-targeting ligand in the design of a polyamidoamine (PAMAM)-based microRNA (miR-15a and miR-16-1) vector to prostate cancer cells. Using polyethyleneglycol (PEG) as a spacer, PAMAM was conjugated to aptamer (PAMAM-PEG-APT) and used as a vehicle for miRNA target delivery. Results: Luciferase assays of pGL-3 expression against PC3 (PSMA − ) and LNCaP (PSMA + ) cells demonstrated that the transfection efficiency of the synthesized DNA/PAMAM-PEG-APT complex was higher than that of the DNA/PAMAM-PEG complex. In addition, cell viability assays of LNCaP (PSMA + ) cells showed that, with a N/P ratio of 15:1, the IC 50 value of miRNA/PAMAM-PEG-APT was approximately 4.7-fold lower than that of miRNA/PAMAM-PEG. Conclusion: This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of prostate cancer cells.

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Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity

Cited by 143 publications

References 27 publications

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

PAMAM dendrimers — diverse biomedical applications. Facts and unresolved questions

Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy

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