RSC Advances
·
2018
·Vol. 8
·期 11
·6053-6062
·
IF 2.936
Tian-Ying Luo,Xi He,Ji Zhang,Ping Chen,Yan-Hong Liu,Hai-Jiao Wang,Xiao-Qi Yu
Carbon dots (CDs) are photoluminescent nanoparticles with distinctive properties, having great potential in nano-biomaterial systems such as gene/drug delivery vectors and cell imaging agents. Fluorine-doped CD C-6F was prepared by a one-step ring-opening polymerization-dehydrative carbonization (RPDC) approach based on low molecular weight polyethyleneimine (PEI, 600 Da) and fluorinated diglycidyl ethers, while the non-fluorinated counterpart C-6H and the CD prepared from PEI 600 Da solely (C-600) were also prepared for comparison. TEM, FT-IR and XPS were performed to determine the compositions and surface states of the CDs. In vitro cell experiment results reveal that the CDs prepared from RPDC approach have much higher transfection efficiency and cellular uptake than PEI 600 contrasts in various cell lines. Compared to non-fluorinated C-6H, C-6F exhibited distinctly higher transfection efficiency, and up to 30 and 260 times higher efficiency than PEI 25 kDa could be achieved in the absence and presence of serum, respectively, indicating the advantage of F-doping. Besides, these CDs exhibit good cell imaging capability under single wavelength excitation, making the materials suitable for cellular tracking and transfection mechanism studies. These results demonstrate that fluorine-doping is an efficient approach to obtained CD gene vectors with high efficiency and serum tolerance.
研究领域:
生物材料
·
纳米医学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Research
·
2021
·
IF 0
Yun Zhou,Mian Yu,Changjun Tie,Yang Deng,Junqing Wang,Yunfei Yi,Fan Zhang,Chenyi Huang,Hairong Zheng,Lin Mei,Meiying Wu
Benefiting from treating diseases at the genetic level, gene therapy has been considered a new revolution in the biomedical field. However, the extracellular and intracellular barriers during gene transport such as enzymatic degradation and endo-/lysosomal sequestration significantly compromise the therapeutic efficacy. Though photochemical internalization (PCI) has emerged as a promising approach for causing endo-/lysosomal leakage with translocation of the internalized molecules into the cytosol, its effect is still unsatisfactory due to the insufficient light penetration depth. Here, we develop tumor microenvironment-specific enhanced gene delivery by means of ROS generated from the in situ cascaded catalytic reactions in tumors involving GOx-mediated redox reaction and Mn2+-mediated Fenton-like reaction. The efficient enzymatic protection and successful endo-/lysosomal escape of cargo gene complexes have been demonstrated. Moreover, anti-Twist siRNA-loaded G@MMSNs-P exhibit tumor-specific biodegradation, excellent T1-weighted MR imaging, and significant inhibitory effects against breast cancer growth and pulmonary metastasis.
研究领域:
医学
·
生物技术
·
癌症治疗
✓ 已验证
DOI
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Yaqiong Wang,Ping Cao,Shicui Li,Xiaofeng Zhang,Jin Hu,Mingyue Yang,Sujuan Yao,Feng Gao,Ao Xia,Jian Shen,Xiaohua Huang
The upconversion luminescence (UCL) marker based on upconversion nanoparticles (UCNPs) shows unique advantages over traditional fluorescence markers, such as enhanced tissue penetration, better photostability, and less autofluorescence . Herein, we constructed a new UCL gene-delivery nonviral vector via layer-by-layer self-assembly of poly(ethylene imine) (PEI) with UCNPs. To reduce the cytotoxicity of PEI, citric acid (CA) was introduced for aqueous modification, and PEI assembly was introduced on the UCNP surface. Our data show that the nonviral vector for UCL gene-delivery demonstrates excellent photostability, low toxicity, and good stability under physiological or serum conditions and can strongly bind to DNA . Moreover, this UCL PEI-based vector could serve as a promising fluorescent gene-delivery carrier for theranostic applications.
研究领域:
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AUSTRALIAN JOURNAL OF CHEMISTRY
·
2015
·Vol. 68
·期 10
·1535-1542
·
IF 1.558
Hao Yu,Shufeng Li,Liandong Feng,Yucheng Liu,Xiaoliang Qi,Wei Wei,Junjian Li,Wei Dong,Hao Yu,Shufeng Li,Liandong Feng,Yucheng Liu,Xiaoliang Qi,Wei Wei,Junjian Li,Wei Dong
Magnetic polyethyleneimine (PEI) complexes have demonstrated to be simple and efficient vectors for enhancing gene transfection. However, the high cytotoxicity of PEI restricts its further application in vivo. In this study, we synthesized several low cytotoxicity biodegradable cationic polymers derived from PEI (Mw 600) linked with diglycidyl tartrate (DT-PEI) or its analogues (diglycidyl succinate (DS-PEI) and diglycidyl malate (DM-PEI); D-PEIs for all 3 polymers). Moreover, a type of biocompatible magnetic nanoparticles (MNPs) with negative charges was prepared to assemble with D-PEIs/DNA complexes via electrostatic interactions. The magnetic ternary complexes have appropriate sizes of 120–150 nm and zeta potential values of ~20–25 mV. The transfection ability and cell viability of D-PEIs increased as the amount of hydroxyl groups increased in the repeat unit, which indicated that increasing the hydroxyl number in the backbone of D-PEIs can enhance gene expression and decrease cytotoxicity in A549 cells. Magnetofection of DT-PEI showed similar transfection efficiency with 30 min incubation; in contrast, the standard incubation time was 4 h. All three magnetic complexes displayed lower cytotoxicity when compared with those of PEI complexes in COS-7 and A549. These results indicated that these series of magnetic PEI derivatives complexes could be potential nanocarriers for gene delivery.
研究领域:
生物医学工程
·
分子生物学
·
材料科学
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 13
·2660-2670
·
IF 4.726
Qian Guo,Yan-Hong Liu,Miao-Miao Xun,Ji Zhang,Zheng Huang,Xue-Dong Zhou,Xiao-Qi Yu
A series of cationic polymers (P1–P5) were designed and synthesized using a ring-opening polymerization strategy based on low molecular weight polyethyleneimine (PEI) and using diglycidyl ethers as the bridging moiety. Although these polymers have reduced amino group density relative to 25 kDa PEI, their pH buffering capacity and deoxyribonucleic acid (DNA) binding ability were seldom affected. They were able to condense plasmid DNA (pDNA) well to form nanoparticles of suitable sizes (150–300 nm) and positive zeta potentials (+25–40 mV). Cell Counting Kit-8 (CCK-8) assays revealed that polyplexes formed from these polymers have lower cytotoxicity than those derived from PEI. Luciferase reporter gene delivery experiments indicated that these polymers have much better transfection efficiency than 25 kDa PEI, especially P2 and P5. Unlike PEI, serum has little negative effect on the transfection by these materials, and their transfection efficiencies were seldom reduced even with high concentrations of serum. Under optimized conditions, up to 400 times higher transfection efficiency than with PEI could be achieved. Several assays including gel electrophoresis, dynamic light scattering and transmission electron microscopy also confirmed the good serum tolerance of these polyplexes. The evenly distributed hydroxyl groups formed by the ring-opening polymerization are considered to contribute much to their high serum tolerance, and such polymerization might be a promising strategy for the design of efficient non-viral gene delivery vectors.
研究领域:
生物化学
·
基因治疗
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 39
·6462-6467
·
IF 4.872
Sheng-Gang Ding,Lei Yu,Long-Hai Wang,Lin-Ding Wang,Zhi-Qiang Yu,Ye-Zi You
Polycations have high DNA condensing ability, low immunogenicity, and great adaptability, which make them promising for gene delivery. However, low transfection efficiency and inevitable toxicity are challenges of cationic polymers. In this study, we prepared a novel Janus dendritic polymer via a one-step Michael addition reaction of branched low-molecular-weight polyethylenimine (PEI, 1800 Da) and dendritic polythioether. The amphiphilic dendritic polymer can self-assemble into stable nanomicelles with high surface charge potential (+91.8 mV). The obtained nanomicelles can be used as a gene delivery vector, which exhibits a higher gene transfection efficiency and much lower cytotoxicity as compared with gold standard PEI (branched, 25 kDa).
研究领域:
生物材料学
·
基因治疗
·
分子生物学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2020
·
IF 5.573
Ya-Ping Xiao,Ji Zhang,Yan-Hong Liu,Zheng Huang,Xiao-Qi Yu
Emulsions have shown great potential in the delivery of various types of cargoes such as nucleic acids and proteins. In this study, fluorinated polymer emulsions ( [email protected] ) were prepared using fluorinated polymers with different structures as surfactant in PFD emulsions under ultrasound. These polymer emulsions gave comparable DNA binding ability compared with corresponding polymers. Heparin competition experiment showed that polymer emulsions could compact DNA or protein to form more stable complexes. In vitro gene transfection results showed that the polymer emulsions could induce higher gene expression than corresponding polymers and polyethyleneimine (PEI), and the transfection efficiency was enhanced with the increase of PFD amount in polymer emulsions. Flow cytometry studies revealed that the emulsions could mediate more efficient cellular uptake with stronger serum tolerance. Moreover, the polymer emulsion could deliver considerable amount of OVA into Raw 264.7 cells at low mass ratio, showing its potential in immunotherapy . The activities of β-galactosidase delivered by the emulsions could also be well maintained after entering cells. This study provides a strategy to construct cationic gene and cytosolic protein vectors with high efficiency and low toxicity.
研究领域:
生物医学工程
·
基因治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Zheru Long,Jun Zhang,Yan Shen,Changren Zhou,Mingxian Liu
Inorganic nanoparticles have attracted much attentions in gene delivery because of their desirable characteristics including low toxicity, well-controlled characteristics, high gene delivery efficiency, and multi-functionalities. Here, natural occurred halloysite nanotubes (HNTs) were developed as a novel non-viral gene vector. To increase the efficiency of endocytosis, HNTs were firstly shortened into an appropriate size (~ 200 nm). Then polyethyleneimine (PEI) was grafted onto HNTs to bind green fluorescence protein (GFP) labeled pDNA. The structure and physical-chemical properties of PEI grafted HNTs (PEI-g-HNTs) were characterized by various methods. PEI-g-HNTs show lower cytotoxicity than PEI. PEI-g-HNTs are positively charged and can bind DNA tightly at designed N/P ratio from 5:1 to 40:1. PEI-g-HNTs/pDNA complexes show much higher transfection efficiency towards both 293T and HeLa cells compared with PEI/pDNA complexes at the equivalent N/P ratio. The transfection efficiencies of PEI-g-HNTs/pDNA complex towards HeLa cell can reach to 44.4% at N/P ratio of 20. PEI-g-HNTs/pDNA complexes possess a higher GFP protein expression than PEI/pDNA from simple western immunoblots. So, PEI-g-HNTs are potential gene vectors with good biocompatibility and high transfection efficiency, which have promising applications in cancer gene therapy.
研究领域:
生物医学工程
·
分子生物学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Kaijin Mai,Shanshan Zhang,Bing Liang,Cong Gao,Wenjun Du,Li-Ming Zhang
To develop new dextran derivatives for efficient gene delivery, the conjugation of poly(amidoamine) dendrons onto biocompatible dextran was carried out by a Cu(I)-catalyzed azide-alkyne cycloaddition, as confirmed by FTIR and 1 H NMR analyses. For resultant dextran conjugates with various generations of poly(amidoamine) dendrons, their buffering capacity and in vitro cytotoxicity were evaluated by acid–base titration and MTT tests, respectively. In particular, their physicochemical characteristics for the complexation with plasmid DNA were investigated by the combined analyses from agarose gel electrophoresis, zeta potential, particle size, transmission electron microscopy and fluorescence emission spectra. Moreover, their complexes with plasmid DNA were studied with respect to their transfection efficiency in human embryonic kidney (HEK293) cell lines. In the case of a higher generation of poly(amidoamine) dendrons, such a dextran conjugate was found to have much lower cytotoxicity and better gene delivery capability when compared to branched polyethylenimine (bPEI, 25 kDa), a commonly used gene vector.
研究领域:
生物化学
·
基因治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2021
·
IF 5.097
Yaqi Cao,Junshi Zhang,Lan Wang,Mingjun Cen,Wenchao Peng,Yang Li,Fengbao Zhang,Juan Tan,Xiaobin Fan
Gene therapy is a revolutionary biomedical technique for the treatment of many diseases, and the development of safe and efficient intracellular gene delivery vectors is crucial for successful gene therapy. Herein, we report a strategy to construct dual-functionalized covalent triazine framework-poly(ethylene glycol)-polyethylenimine (CTF-PEG-PEI) nanosheets as nonviral vectors via exfoliation and surface chemistry modification. Benefiting from the unique brushlike hierarchical structure, CTF-PEG-PEI can strongly condense nucleic acids and efficiently release the nucleic acid cargo after cellular uptake. Systematic gene delivery studies in both 293T and HeLa cells demonstrate that CTF-PEG-PEI has superior gene transfection performance and lower cytotoxicity compared with polyethylenimine (PEI), especially at low dosages.
研究领域:
生物医学工程
·
基因治疗
·
材料科学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Maohua Chen,Yun Zhang,Zhoujiang Chen,Songzhi Xie,Xiaoming Luo,Xiaohong Li
Challenges remain to load and deliver two or multiple drugs of complementary effects for synergistic cancer therapies. In the current study, multiarmed amphiphilic copolymers of 4-arm poly(ethylene glycol) (PEG) and polyaspartate (PAsp) are created for conjugation of camptothecin (CPT) and condensation with tumor necrosis factor-α (TNF) plasmids. Diethylenetriamine (DET) is grafted on PAsp, and CPT is conjugated onto PAsp(DET) by disulfide linkages to form hydrophobic cores of micelles , followed by condensation with TNF plasmids to form micelleplexes. The cis -aconitic linkers are introduced between PEG and PAsp(DET) to remove PEG shells in response to acidic pH, resulting in destabilized micelleplexes and prompted endosomal escape into the cytosol. The micelleplex disintegration in response to reductive stimuli in the cytosol leads to an efficient CPT release and pDNA disassociation. The co-delivery of CPT with TNF plasmids enhances the gene transfection of micelleplexes at low N/P ratios, and shows synergetic cytotoxicities to tumor cells with 2.5 and 8 folds lower IC 50 s compared with those after treatment with CPT or TNF alone, respectively. The micelleplex treatment on 4T1 tumor models dramatically extends the animal survival and suppresses the tumor growth with 2.3 and 3 folds lower in volume compared with CPT or TNF treatment alone, respectively. Histological and biochemical analyses display TNF expressions in tumor tissues after micelleplex treatment, resulting in significantly larger necrotic regions in tumors, higher cell apoptosis rates , and no obvious sign of tumor metastasis in lungs compared with other treatment. Therefore, the multifunctional micelleplexes based on multiarmed PEG-PAsp(DET) copolymers offer the targeted drug/gene delivery, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promises for combination therapies. Statement of Significance Micelleplexes are constructed from multiarmed amphiphilic copolymers with conjugation of captothecin (CPT) and condensation of tumor necrosis factor-α (TNF) plasmid. The pH/redox stimuli realize co-delivery of CPT and pDNA in a sequential manner of folate-mediated endocytosis , endosomal escape induced by PEG cleavage, reduction-sensitive release of CPT in cytosol, and pDNA release from disintegrated polyplexes after CPT release. Compared with CPT or TNF treatment alone, the micelleplexes achieve 2.5 and 8 folds higher cytotoxicities to tumor cells, and suppress the tumor growth with 2.3 and 3 folds lower in volume, respectively. It demonstrates a feasible strategy to develop multifunctional micelleplexes with simultaneous drug conjugation and pDNA condensation, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promise for combinational therapies.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2013
·Vol. 10
·期 5
·980-988
·
IF 7.823
Shengwang Zhou,Xuezhong Du,Fangbo Cui,Xianfeng Zhang
Novel DNA-gated mesoporous silica nanoparticle (MSN) vehicles functionalized with disulfide-linked acridinamine intercalators are constructed for multi-responsive controlled release. The DNA-gated MSN vehicles release cargo encapsulated in the MSN pores under different stimuli, including disulfide reducing agents, elevated temperature, and deoxyribonuclease I (DNase I), for codelivery of drugs and DNA/genes in different forms. Furthermore, the cascade release of encapsulated and intercalative drugs is controlled by AND logic gates in combination of dual stimuli. The ingeniously designed DNA-gated MSN vehicles integrates multiple responses and AND logic gate operations into a single smart nanodevice not only for codelivery of drugs and DNA/genes but also for cascade release of two drugs and has promising biological applications to meet diverse requirements of controlled release.
研究领域:
纳米医学
·
生物材料
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）