Evaluation of polyethylene glycol-conjugated novel polymeric anti-tumor drug for cancer therapy

Nam, Joung-Pyo; Park, Jun-Kyu; Son, Donghee; Park, Sun-Jeong; Park, Seong-Cheol; Choi, Changyong; Jang, Mi-Kyeong; Nah, Jae‐Woon

doi:10.1016/j.colsurfb.2014.04.013

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…Figure 2a–c show the 1 H-NMR spectra of DHA, 8arm-PEG–DHA and TF-8arm-PEG–DHA, where the signals at 0.80–2.90 are attributed to the most characteristic peak protons of DHA 33 , those at 3.40–3.85 (4 nH, –(CH2CH2O)n–) and 4.20 (2H, –CH2OC(O)O–) to the methylene protons of PEG, and those at 0.81–1.30 are attributed to the proton peaks of TF 34 . The doublet around 4.78 (1H, CH) of DHA moving to 5.82 (1H, CH) in 8arm-PEG-DHA spectra indicated successful synthesis of ester bonds between PEG and DHA.…”

Section: Resultsmentioning

confidence: 99%

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Liu

Dai

et al. 2016

Sci Rep

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Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol–dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG–DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.

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Section: Resultsmentioning

confidence: 99%

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Liu

Dai

et al. 2016

Sci Rep

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“…As shown in Figure 1, the peak assignments of poly(CBA-DAH), PEI 1.8 kDa, and PCDP were classified in the data. In the NMR data of PCDP, the proton peaks of poly(CBA-DAH) and PEI were shifted downfield due to steric hindrance caused by the conjugation between poly(CBA-DAH) and PEI (J. P. Nam et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Design of PEI-conjugated bio-reducible polymer for efficient gene delivery

Nam

Kim

2018

International Journal of Pharmaceutics

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The poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)) was designed previously as a bio-reducible efficient gene delivery carrier. However, the high weight ratio required to form the polyplexes between poly(CBA-DAH) with pDNA is still a problem that needs to be addressed. To solve this problem and increase the transfection efficiency, poly(ethylenimine) (PEI, 1.8 kDa) was conjugated to poly(CBA-DAH) via disulfide bond. The PEI conjugated poly(CBA-DAH) (PCDP) can bind with pDNA at a very low weight ratio of 0.5 and above, like PEI 25 kDa, and form the polyplexes with nano-size (102-128 nm) and positive surface charge (27-34 mV). PCDP and PCDP polyplexes had negligible cytotoxicity and indicated similar or better cellular uptake than the comparison groups such as PEI 25 kDa and Lipofectamine® polyplexes. To confirm the transfection efficiency, the plasmid DNA (pDNA) encoded with the luciferase reporter gene (gWiz-Luc) and green fluorescent protein reporter gene (GFP) were used and treated with PCDP into the A549, Huh-7, and Mia PaCa-2 cells. PCDP/pDNA polyplexes showed highest transfection efficiency in all tested cell lines. In the luciferase assay, PCDP polyplexes showed 10.2 times higher gene transfection efficiency than Lipofectamine® polyplexes in mimic in vivo conditions (30% FBS, A549 cells). The VEGF siRNA expressing plasmid (pshVEGF), which is constructed as a therapeutic gene by our previous work, was delivered by PCDP into the cancer cells. The VEGF gene expression of PCDP/pshVEGF polyplexes was dramatically lower than control and the VEGF gene silencing efficiencies of PCDP/pshVEGF (w/w; 10/1) polyplexes were 54% (A549 cells), 77% (Huh-7 cells), and 66% (Mia PaCa-2 cells). In addition, PCDP/pshVEGF had reduced cell viability rates of about 31% (A549 cells), 39% (Huh-7 cells), and 42% (Mia PaCa-2 cells) and showed better results than all comparison groups. In the transfection efficiency and VEGF silencing assay, PCDP polyplexes showed better results than poly(CBA-DAH) at 4-fold lower weight ratio. The data of all experiments demonstrate that the synthesized PCDP could be used for efficient gene delivery and could be widely applied.

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“…Aiming to prepare a biodegradable gene vector with high transfection efficiency and low cytotoxicity, it had conjugated low molecular weight (LMW) PEIs to the biodegradable backbone polyglutamic acids derivative (PEG-b-PBLG) by aminolysis to form PEIs combined PEG-b-PLG-g-PEIs [94]. A series of tri-block copolymers, PEG-g-PEI-g-poly (dimethylaminoethyl Lglutamine) (PEG-g-PEI-g-PDMAEG), as novel vectors for gene therapy was synthesized and evaluated [95]. The synthesized PEG-g-PEI-g-PDMAEG tri-block copolymers are promising candidates as non-viral carriers for gene delivery.…”

Section: Polyethylenimine Copolymersmentioning

confidence: 99%

Recent advances in polymeric drug delivery systems

2020

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Background: Polymeric drug delivery systems have been achieved great development in the last two decades. Polymeric drug delivery has defined as a formulation or a device that enables the introduction of a therapeutic substance into the body. Biodegradable and bio-reducible polymers make the magic possible choice for lot of new drug delivery systems. The future prospects of the research for practical applications has required for the development in the field. Main body: Natural polymers such as arginine, chitosan, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid have been treated for polymeric drug delivery systems. Synthetic polymers such as poly (2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide)s, poly(ethylenimine)s, dendritic polymers, biodegradable and bio-absorbable polymers have been also discussed for polymeric drug delivery. Targeting polymeric drug delivery, biomimetic and bio-related polymeric systems, and drug-free macromolecular therapeutics have also treated for polymeric drug delivery. In polymeric gene delivery systems, virial vectors and non-virial vectors for gene delivery have briefly analyzed. The systems of non-virial vectors for gene delivery are polyethylenimine derivatives, polyethylenimine copolymers, and polyethylenimine conjugated bio-reducible polymers, and the systems of virial vectors are DNA conjugates and RNA conjugates for gene delivery. Conclusion: The development of polymeric drug delivery systems that have based on natural and synthetic polymers are rapidly emerging to pharmaceutical fields. The fruitful progresses have made in the application of biocompatible and bio-related copolymers and dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs. Combining perspectives from the synthetic and biological fields will provide a new paradigm for the design of polymeric drug and gene delivery systems.

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Evaluation of polyethylene glycol-conjugated novel polymeric anti-tumor drug for cancer therapy

Cited by 11 publications

References 33 publications

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Design of PEI-conjugated bio-reducible polymer for efficient gene delivery

Recent advances in polymeric drug delivery systems

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