Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

The principal impediment to gene therapy is the development of efficient, nontoxic gene carriers that can handle and deliver foreign genetic materials into various cell types, including healthy and cancerous cells. Poly-l-lysine (PLL) polymers are one of the most favorable gene carriers among nonviral vectors, and PLL had low transfection and safety issues. The purpose of this study was to measure cellular toxicity, DNA damage, and apoptotic effects of PLL nanoparticles. Neuro2A mammalian cells were cultured and exposed to PLL/DNA complexes at different polymer/DNA ratios ( C/ P ratio 2 and 6) for 24 h. To evaluate metabolic activity, genotoxicity, and apoptotic influences of PLL nanoparticle, the following experimental methods were employed, in order: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), DNA damage (COMET analysis) assay, and sub-G1 peak apoptosis assay. Our data indicate that toxicity is concentration dependent and a high concentration of polymer declined the metabolic activity. In addition, largest complexes ( C/ P 6 in HEPES buffered saline buffer) have slighter negative impact on metabolic activity. In agreement with our cytotoxicity data, apoptotic assay result represented that increase in size of PLL/DNA complexes decrease the number of apoptotic cells. Also, there was a remarkable increase in percent tail DNA of Neuro2A cells treated with higher concentration of PLL and its polyplexes. The present study demonstrated that PLL/DNA complexes caused cytotoxic, apoptotic, and genotoxic effects in a dose-dependent and weight ratio-dependent manner, which also affected the size of polyplexes.

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“…Besides, HEPES buffered saline (HBS; 20-mM HEPES, 5.2% glucose, 0.5-M sodium chloride (NaCl), pH 7.2) was applied for larger polyplexes. 30…”

Section: Cell Culturementioning

confidence: 99%

Evaluation and comparison of cytotoxicity, genotoxicity, and apoptotic effects of poly-l-lysine/plasmid DNA micro- and nanoparticles

et al. 2019

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“… 2005 ; Alavi et al. 2017 ). Owing to their defined molecular structure and variable functional groups located on their outer surfaces and inner moieties, dendrimers are proper platforms for the development of biopharmaceuticals as well as nanomedicine carriers (Inoue 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Malaekeh‐Nikouei

Rezaee

Gholami

et al. 2018

Pharmaceutical Biology

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Context: Polypropylenimine (PPI), a cationic dendrimer with defined structure and positive surface charge, is a potent non-viral vector. Dexamethasone (Dexa) conveys to the nucleus through interaction with its intracellular receptor. Objective: This study develops efficient and non-toxic gene carriers through conjugation of Dexa at various percentages (5, 10 and 20%) to the fourth and the fifth generation PPIs (PPIG4s and PPIG5s). Materials and methods: The 21-OH group of Dexa (0.536 mmol) was modified with methanesulfonyl chloride (0.644 mmol) to activate it (Dexa-mesylate), and then it was conjugated to PPIs using Traut's reagent. After dialysis (48 h) and lyophilization, the physicochemical characteristics of products (PPI-Dexa) including zeta potential, size, buffering capacity and DNA condensing capability were investigated and compared with unmodified PPIs. Moreover, the cytotoxicity and transfection activity of the Dexa-modified PPIs were assessed using Neuro2A cells. Results: Transfection of PPIG4 was close to PEI 25 kDa. Although the addition of Dexa to PPIG4s did not improve their transfection, their cytotoxicity was improved; especially in the carrier to DNA weight ratios (C/P) of one and two. The Dexa conjugation to PPIG5s enhanced their transfection at C/P ratio of one in both 5% (1.3-fold) and 10% (1.6-fold) Dexa grafting, of which the best result was observed in PPIG5-Dexa 10% at C/P ratio of one. Discussion and conclusions: The modification of PPIs with Dexa is a promising approach to improve their cytotoxicity and transfection. The higher optimization of physicochemical characteristics, the better cell transfection and toxicity will be achieved.

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“…Nanoparticles, because of their small size and unique optical, biological, and chemical properties possess wide application in biotechnology and medicine [4][5][6]. Quantum dots (QDs) are an example of this type.…”

Section: Introductionmentioning

confidence: 99%

Mn‐doped ZnS quantum dots‐chlorin e6 shows potential as a treatment for chondrosarcoma: an in vitro study

Mohsenian

Shanei

Alavi

et al. 2019

IET nanobiotechnol.

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Chondrosarcoma is the second-most malignant cancer of the bone and routine treatments such as chemotherapy and radiotherapy have not responded to the treatment of this cancer. Due to the resistance of chondrosarcoma to radiotherapy, the combination of therapeutic methods has been considered in recent years. In this study, a novel combination approach is used that allows photodynamic therapy to be activated by X-rays. The synthesis of Mn-doped zinc sulphide (ZnS) quantum dots was carried out and chlorin e6 photosensitiser attached by covalent and non-covalent methods and their application as an intracellular light source for photodynamic activation was investigated. The toxicity of each nanoparticles was evaluated on chondrosarcoma cancer cells (SW1353) before and after radiation. Also, the effect nanoparticle-photosensitiser conjugated type was investigated in the therapeutic efficacy. The characterisation test (SEM, TEM, EDS, TGA, XRD and ICP analyses) was shown successful synthesis of Mn-doped ZnS quantum dots. Chondrosarcoma cancer cell viability was significantly reduced when cells were treated with MPA-capped Mn-doped ZnS quantum dots-chlorin e6 with spermine linker and with covalent attachment (P ≤ 0.001). These results indicate that X-ray can activate the quantum dot complexes for cancer treatment, which can be a novel method for treatment of chondrosarcoma.

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Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

Cited by 10 publications

References 51 publications

Evaluation and comparison of cytotoxicity, genotoxicity, and apoptotic effects of poly-l-lysine/plasmid DNA micro- and nanoparticles

Evaluation and comparison of cytotoxicity, genotoxicity, and apoptotic effects of poly-l-lysine/plasmid DNA micro- and nanoparticles

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Mn‐doped ZnS quantum dots‐chlorin e6 shows potential as a treatment for chondrosarcoma: an in vitro study

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