Polyethylenimine-grafted polyamidoamine conjugates for gene delivery with high efficiency and low cytotoxicity

Kim, Tae-Hun; Seo, Ho Won; Han, Jin; Ko, Kyung Soo; Choi, Joon Sig

doi:10.1007/s13233-014-2108-8

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…PAMAM dendrimers are a class of synthetic star-burst polymers that possess well-defined structures as well as desirable properties such as non-toxicity, non-immunogenicity, and excellent water solubility. Their active terminal functional groups allow for chemical modification and bioconjugation to various bioactive molecules, enabling their use in diverse medical applications including cancer targeting and treatment, 35,36 drug delivery, 21,37 gene delivery, 38,39 photodynamic therapy, 40,41 sensors, 42,43 and imaging. 44,45 Furthermore, PAMAM dendrimers have been recognized for their ability to enhance water solubility of hydrophobic drug molecules.…”

Section: Resultsmentioning

confidence: 99%

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Bi,

Watts,

Dorman

et al. 2023

J Biomater Appl

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The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%–80% of their loads in 1–4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Bi,

Watts,

Dorman

et al. 2023

J Biomater Appl

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“…Employing polycations to condense polyanionic DNA is an important prerequisite for gene delivery (7,29). Appearance of the peak at 1485 cm -1 was important evidence to confirm PEI was successfully grafted onto the CNC surface to form a polycationic-CNC nanoparticle (30).…”

Section: Discussionmentioning

confidence: 99%

Fabrication and Optimization of Linear PEI-Modified Crystal Nanocellulose as an Efficient Non-Viral Vector for In-Vitro Gene Delivery

et al. 2020

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Background: One of the major challenges in gene therapy is producing gene carriers that possess high transfection efficiency and low cytotoxicity (1). To achieve this purpose, crystal nanocellulose (CNC)-based nanoparticles grafted with polyethylenimine (PEI) have been developed as an alternative to traditional viral vectors to eliminate potential toxicity and immunogenicity. Methods: In this study, CNC-PEI10kDa (CNCP) nanoparticles were synthetized and their transfection efficiency was evaluated and compared with linear cationic PEI10kDa (PEI) polymer in HEK293T (HEK) cells. Synthetized nanoparticles were characterized with AFM, FTIR, DLS, and gel retardation assays. In-vitro gene delivery efficiency by nano-complexes and their effects on cell viability were determined with fluorescent microscopy and flow cytometry. Results: Prepared CNC was oxidized with sodium periodate and its surface cationized with linear PEI. The new CNCP nano-complex showed different transfection efficiencies at different nanoparticle/plasmid ratios, which were greater than those of PEI polymer. CNPC and Lipofectamine were similar in their transfection efficiencies and effect on cell viability after transfection. Conclusions: CNCP nanoparticles are appropriate candidates for gene delivery. This result highlights CNC as an attractive biomaterial and demonstrates how its different cationized forms may be applied in designing gene delivery systems.

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“…The modified nanoparticles are of low cytotoxicity and high gene transfection efficiency in comparison with the original ones. Apart from modification using these small molecules, numerous polymers (e.g., PEG, 26,43,44 polyalanine, 28,45 HPEG, 46 polyphenylalanine, 45 polyglycerol, 47 polylysine, 48 PAMAM, 49 polyĲγ-benzyl-Lglutamate) 50,51 and polyĳN-(2-hydroxyethyl)-L-glutamine] 52 ) are also employed. Surprisingly, Zhu and coworkers found that even HPEGs prepared via a one-pot Michael addition reaction of 2,20-(ethylenedioxy)bis-(ethylamine) (EOBEA) and poly-Ĳethylene glycol) diacrylate (PEGDA) further end-capped with diethylamine with low charge density still exhibited high transfection efficiency in a COS-7 cell line in the absence and presence of serum.…”

Section: Biocompatibilitymentioning

confidence: 99%

Designing hyperbranched polymers for gene delivery

Mou

Jin

et al. 2016

Mol. Syst. Des. Eng.

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Polyethylenimine-grafted polyamidoamine conjugates for gene delivery with high efficiency and low cytotoxicity

Cited by 8 publications

References 26 publications

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Fabrication and Optimization of Linear PEI-Modified Crystal Nanocellulose as an Efficient Non-Viral Vector for In-Vitro Gene Delivery

Designing hyperbranched polymers for gene delivery

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