All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control

Park, Kyong Mi; Kang, Han Chang; Cho, Jung Kyo; Chung, Ik Joo; Cho, Sang‐Hee; Bae, You Han; Na, Kun

doi:10.1016/j.biomaterials.2009.01.025

Cited by 30 publications

(31 citation statements)

References 39 publications

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“…The ATRAe Low PEI conjugates were synthesized according to our previous reports [14,22]. Briefly, a mixture of ATRA (40 mg, 133 mmol), DCC (41 mg, 200 mmol), and NHS (23 mg, 200 mmol) was dissolved in DMSO (10 mL) and stirred for 3 h. After the Low PEI (0.2 g, 111 mmol) was completely dissolved in DMSO, the two solutions were stirred for 24 h. The resultant solution was filtered to eliminate any insoluble dicyclohexylurea, and the filtrate was dialyzed against distilled water (DW) for 3 days using a dialysis membrane (Molecular weight cut-off, MWCO: 1.0 kDa).…”

Section: Synthesis and Characterization Of The Atrae Low Pei Conjugatesmentioning

confidence: 99%

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

et al. 2014

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Section: Synthesis and Characterization Of The Atrae Low Pei Conjugatesmentioning

confidence: 99%

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

et al. 2014

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“…34,35 On the other hand, the cytotoxic mechanism of PeRA led to nano-hole formation on the cell surface. 27 Cationic polymers such as PEI, poly-L-lysine, and poly(amidoamine) dendrimers form nano-holes on the cell membrane via a charge interaction between the positively charged polymer and the negatively charged cell membrane. [36][37][38][39] The nano-holes not only enhance the membrane permeability of the material, 36-41 but also promote cell death.…”

Section: Resultsmentioning

confidence: 99%

“…The synthesis of PEI/ ATRA (PeRA) conjugates via DCC-and HOSU-mediated amide formation between the primary amines of PEI and a carboxyl acid of all-trans retinoic acids (ATRAs) was already reported by our group. 27 In brief, PEI (1 g) and ATRA (125 mg) were dissolved in DMSO (20 mL) for 3 h. DCC and HOSU as coupling reagent and catalyst (molar ratio of PEI to catalyst=1:1.2), respectively, were added in the DMSO solution and vigorously stirred for 12 h. The resultant PEI/ATRA conjugate (PeRA) was poured into a dialysis membrane (MWCO: 3,500) and dialyzed against distilled water for 3 days. 28 To obtain the degree of substitution, the absorbance of the solutions were measured by UV-vis spectrophotometer at room temperature.…”

Section: Methodsmentioning

confidence: 97%

Development of a new micellar anticancer drug: Cationic polymer/vitamin A conjugate covered with hyaluronic acid

Yim

2010

Macromol. Res.

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This study examined the development of a new micellar drug (MD) prepared from polyethylenimine (PEI)/vitamin A (all trans-retinoic acid; ATRA) conjugate (PeRA) for the treatment of cancer. To endow specific toxicity to cancer cells, PeRA was coated with hyaluronic acid (anionic polymer; HA), which enhanced the biocompatibility of PeRA and was easily degraded by the enzyme secreted from the tumor site. The physicochemical results suggest that HA covered the micelles well via a charge-charge interaction. The cytotoxicity of PeRA measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay varied according to the presence or absence of the HA degrading enzyme (HAase). When the enzyme was absent, PeRA-HA showed lower cytotoxicity against cancer cells but the cytotoxicity was increased dramatically in the presence of the HAase. To define the cytotoxic mechanism, the interactions between PeRA and the cells were observed by flow cytometry (FACS) and confocal microscopy. The results showed that nano-hole formation induces cytotoxicity via an electrostatic interaction between PeRA and cell surfaces. This suggests that a HA shielded PEI micelle system might be a viable alternative for the development of anticancer agents.

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“…28 Novel approaches were developed using polymeric gene carriers conjugated with all-trans-retinoic acid (ATRA). 29 Target ligands that are stable, small, and have cell-nuclear localization ability are of interest to researchers.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, researchers are currently interested in investigating cationic gene vectors that can locate in cell nuclei. 29,63,64 Using PG6-PEI25k as the platform, the ability of the PG6-PEI-INO polymers to enter cell nuclei and to mediate efficient transgene expression was found to increase with their INO moiety numbers, as reported by fluorescent tracking and EGFP expression. Therefore, the INO might be a potential ligand for efficient transgene expression.…”

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confidence: 99%

Using inositol as a biocompatible ligand for efficient transgene expression

Zhang¹,

Bellis²,

Fan³

et al. 2015

IJN

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Transgene transfection techniques using cationic polymers such as polyethylenimines (PEIs) and PEI derivatives as gene vectors have shown efficacy, although they also have shortcomings. PEIs have decent DNA-binding capability and good cell internalization performance, but they cannot deliver gene payloads very efficiently to cell nuclei. In this study, three hyperbranched polyglycerol-polyethylenimine (PG6-PEI) polymers conjugated with myo-inositol (INO) molecules were developed. The three resulting PG6-PEI-INO polymers have an increased number of INO ligands per molecule. PG6-PEI-INO 1 had only 14 carboxymethyl INO (CMINO) units per molecule. PG6-PEI-INO 2 had approximately 130 CMINO units per molecule. PG6-PEI-INO 3 had as high as 415 CMINO units approximately. Mixing PG6-PEI-INO polymers with DNA produced compact nanocomposites. We then performed localization studies using fluorescent microscopy. As the number of conjugated inositol ligands increased in PG6-PEI-INO polymers, there was a corresponding increase in accumulation of the polymers within 293T cell nuclei. Transfection performed with spherical 293T cells yielded 82% of EGFP-positive cells when using PG6-PEI-INO 3 as the vehicle. Studies further revealed that extracellular adenosine triphosphate (eATP) can inhibit the transgene efficiency of PG6-PEI-INO polymers, as compared with PEI and PG6-PEI that were not conjugated with inositol. Our work unveiled the possibility of using inositol as an effective ligand for transgene expression.

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All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control

Cited by 30 publications

References 39 publications

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

Development of a new micellar anticancer drug: Cationic polymer/vitamin A conjugate covered with hyaluronic acid

Using inositol as a biocompatible ligand for efficient transgene expression

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All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control

Cited by 30 publications

References 39 publications

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

Development of a new micellar anticancer drug: Cationic polymer/vitamin A conjugate covered with hyaluronic acid

Using inositol as a biocompatible ligand for&nbsp;efficient transgene expression

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Using inositol as a biocompatible ligand for efficient transgene expression