Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 7
·1482-1497
·
IF 4.543
Xiaobing Chen,Jun Yang,Hong Liang,Qian Jiang,Bowen Ke,Yu Nie
Integrating the advantages of artificial vectors with bioinspired strategies has opened interesting perspectives in the design of gene delivery systems. Herein, disulfide modified, self-assembled lipopeptides with arginine-rich periphery are demonstrated as gene vectors (RLS). It is surprising that these carriers achieved excellent gene transfection efficacy (up to 380-fold higher than PEI) in different cell lines (HeLa and B16 cells) at relatively low N/P (∼10) ratios, compared to the analog lipopeptides without disulfide bonds (RL, N/P 40). As shown from the morphologies observed by transmission electronic microscopy and surface charge detection by dynamic light scattering, the existence of disulfide bonds may influence the configuration/conformation of the RLS assembly with decreased zeta potential (+27.2 mV), compared to that of the analogs, RL (+46.5 mV). Correspondingly, RLS/DNA complexes showed relatively lower zeta potentials than those of RL/DNA complexes at different N/P ratios. Under the transfection conditions, RLS/DNA complexes (N/P 10) showed even less cellular uptake than that of RL/DNA complexes (N/P 40), and no difference was detected in buffering effect and endosomal escape between RLS and RL complexes. Examination by gel electrophoresis and fluorescence resonance energy transfer (FRET) images in cell culture conditions confirmed that RLS lipoplexes could effectively liberate DNA. Thus, the higher gene transfection efficiency of disulfide modified vectors might be mainly attributed to the cleavage of disulfide bonds; the rapid release of DNA and the superiority of the design was closely related to the reductive conditions in the cells.
研究领域:
生物化学
·
分子生物学
·
药物递送
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 90
·73416-73423
·
IF 3.84
Yanan Xue,Xiaoyang Xia,Bo Yu,Xiaogang Luo,Ning Cai,Sihui Long,Faquan Yu
A surfactant-free and organic solvent-free one-pot method was utilized for the preparation of a pH-responsive alginate nanogel (pH-AN). Simply by mixing anionic sodium alginate (SA) with cationic doxorubicin (DOX) through electrostatic interactions, followed by in situ crosslinking with ionic calcium under ultrasound, a DOX-loaded pH-AN was obtained. The sizes of the nanogels can be tailored by varying the concentration of SA, the ratio of SA to ionic calcium and DOX. The nanogel was measured with a size range of 210 nm, and a polydispersity index of 0.208, as confirmed by transmission electron microscopy and dynamic light scattering. In vitro release profiles showed a significantly higher accumulative release at pH 5.0 than at pH 7.4, exhibiting apparent acid responsiveness. In vitro cytotoxicity tests clearly illustrated the remarkable inhibition to the growth of HeLa cells with an IC50 value of 0.26 μg mL−1. In contrast, NIH 3T3 cells displayed high tolerance. The plain nanogel exclusive of DOX was practically non-toxic. Confocal laser scanning microscopy observation demonstrated that DOX was efficiently internalized into HeLa cells through endocytosis, released into the cytoplasm, and then principally entered the nuclei. It is clearly suggested that a green and facile method was proposed to achieve a pH-responsive nanogel carrier for the delivery of drugs.
研究领域:
药剂学
·
生物材料
·
肿瘤学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2013
·Vol. 4
·期 8
·2489-2495
·
IF 5.231
Yajuan Sun,Weibing Dong,Huiyuan Wang,Yongzhuo Huang,Huike Gu,Victor C. Yang,Junbo Gong
Nanorods are capable of enhanced intracellular delivery and prolonged blood circulation over their spherical counterparts, and thus can be used as unmatched drug carriers for cancer chemotherapy. An innovative method was developed to synthesize size-tunable, PMAA@chitosan-based, hollow polymeric nanorods for intracellular delivery, by using mesoporous silica nanorod templates. The morphology of the polymeric hollow nanorods was examined by TEM and FT-IR spectra, which indicated a homogeneous three-dimensional structure. An uptake study using human lung carcinoma A-549 cell lines revealed highly efficient cell internalization of the FITC-labeled nanorods, suggesting the potential of utilizing these nanorods as carriers in achieving effective intracellular drug delivery. Cell viability studies of the docetaxel-loaded nanorods yielded consistent results, as the drug-loaded nanorods produced a significantly higher inhibition of the growth of A-549 tumor cells when compared with treatment by free docetaxel. Overall, this preliminary in vitro investigation sheds light on the use of prepared hollow polymeric nanorods for drug delivery applications.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2013
·Vol. 5
·期 3
·854-861
·
IF 5.231
Haibo Wang,Yin Wang,Yangjun Chen,Qiao Jin,Jian Ji
A biodegradable and endosomal pH-sensitive polymeric prodrug poly(5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one)-graft-12-acryloyloxy dodecyl phosphorylcholine-co-6-maleimidocaproyl-doxorubicin (PMAC-graft-(ADPC-co-Mal-DOX) was synthesized by ring-opening polymerization (ROP) and “click” reaction. DOX was conjugated to the polymer by hydrazone bonds which would result in a pH-sensitive controlled release of drug. The polymeric prodrug can form a self-assembled micellar structure which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Flow cytometry and fluorescence microscopy results demonstrated that prodrug micelles could be internalized by cancer cells remarkably. In vitro drug release studies showed that the release of DOX was faster at endosomal pH (pH = 5.0) than at normal physiological environment (pH = 7.4). Moreover, this prodrug exhibited high cytotoxicity against HepG2 cells and HeLa cells, indicating its great potential for cancer therapy.
研究领域:
药物递送系统
·
高分子化学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
TALANTA
·
2022
·
IF 6.556
Miaosen Zhang,Shan He,Wei Pang,Wei Wei,Feng Zhou,Xiaoyu Wu,Hang Qi,Xuexin Duan,Yanyan Wang
Currently, researches on nanomaterials have been restricted by slow and multistep synthesis procedures. Herein, we demonstrate an ultrafast, one step method of purification and delivery of quantum dots into living cells, actuated by the acoustic streaming (AS) produced through a gigahertz resonator. Results demonstrate that the impurities in the carbon dots (CDs) can be extracted immediately aided by the acoustic forcing, with extra high purification efficiency of 93%. The system can also efficiently deliver the CDs into cells, showing excellent nucleus and mitochondria uptake under 3 min of AS treatment, and making the organelles of cells to be recorded more easily and simultaneously. More importantly, the AS is found to further accelerate the bioreaction inside the cells, thus realizes the enhanced biosensing of Fe 3+ in single living cells. This work develops a novel type of multifunctional method for effective purification, intracellular delivery and biosensing of nanomaterials, inspiring the biological/medical nanotechnology researches at subcellular level.
研究领域:
纳米技术
·
生物成像
·
生物传感
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano-Micro Letters
·
2019
·Vol. 11
·期 1
·1-16
·
IF 9.043
Xin Xiaofei,Du Xiaoqing,Xiao Qingqing,Azevedo Helena S.,He Wei,Yin Lifang
Nanosized cytotoxic drug could combat against the autophagy induced by the drug.
The drug nanorods enabled efficient intracellular delivery of the nucleic acid and the resultant autophagy inhibition in vitro and in vivo, which in turn sensitized the cancer cells to the anti-tumor nanorods.
研究领域:
药理学
·
纳米技术
·
癌症生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2016
·
IF 4.342
Meirong Huo,Yao Liu,Lei Wang,Tingjie Yin,Chen Qin,Yanyu Xiao,Lifang Yin,Jiyong Liu,Jianping Zhou
A redox-sensitive micellar system constructed from an O,N-hydroxyethyl chitosan–octylamine (HECS-ss-OA) conjugate with disulfide linkages between the hydrophobic alkyl chains and hydrophilic chitosan backbone was synthesized for triggered intracellular delivery of hydrophobic paclitaxel (PTX). In aqueous environments, conjugates formed micelles with high PTX loading (>30%). Mechanistically, the sensitivity of HECS-ss-OA micelles to reducing environments was investigated using the parameters of in vitro release and particle size. Intracellular release of nile red fluorescence alongside cytotoxicity studies further confirmed the potency of redox-sensitive micelles for intracellular drug delivery compared with redox-insensitive micelles. Additionally, an in vivo study confirmed the efficacy of PTX-loaded micelles in tumor-bearing mice with superior antitumor efficacy and diminished systemic toxicity when compared with the redox-insensitive micelles and a PTX solution. These results demonstrate the potential of redox-sensitive HECS-ss-OA micelles for intracellular trafficking of lipophilic anticancer drugs.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Tingting Luo,Jingtian Han,Feng Zhao,Xiaohong Pan,Baocheng Tian,Xiujuan Ding,Jing Zhang
Novel chitosan-cystamine-retinoic acid conjugate (CS-SS-RA) was synthesized and could self-assemble into redox-sensitive micelles in aqueous environment with low critical micelle concentration value. CS-SS-RA micelles were characterized with spherical shape, desirable particle size, negative zeta potential, high paclitaxel (PTX) loading and encapsulation efficiency and redox-sensitivity. Hemolysis and cytotoxicity studies proved the safety of CS-SS-RA micelles for intravenous administration. Cytotoxicity study against HepG2 cells and the growth inhibition study on three-dimensional multicellular tumor spheroids (MCTSs) revealed that PTX-loaded CS-SS-RA micelles exhibited higher antitumor activity than free PTX. The in vitro cellular uptake profiles of FITC-labeled CS-SS-RA micelles evaluated via confocal laser scanning microscopy and flow cytometry indicated that CS-SS-RA micelles could enhance cellular uptake efficiency of PTX, and their internalization by HepG2 cells were mediated by clathrin-mediated endocytosis and macropinocytosis. These results demonstrated that CS-SS-RA micelles could be developed as a promising platform for intracellular delivery of hydrophobic antitumor agents.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Kuiyu Meng,Dongmei Chen,Fei Yang,Aoxue Zhang,Yanfei Tao,Wei Qu,Yuanhu Pan,Haihong Hao,Shuyu Xie
Four fatty acid-solid lipid nanoparticles (SLNs) were formulated and evaluated for intracellular delivery, accumulation, as well as discrepancy in antimicrobial efficacy of their loaded enrofloxacin by using RAW 264.7 cells. The delivery efficacy of enrofloxacin into the macrophages by docosanoic acid SLNs (DAS), octadecanoic acid SLNs (OAS), hexadecanoic acid SLNs (HAS), and tetradecanoic acid SLNs (TAS) were 26.1 – 29.0, 9.3–10.3, 4.7–5.3 and 4.5 – 5.0 folds, respectively, compared to free drug when co-incubation for 0.25−4 h. The longer fatty acid prepared nanoparticles loaded enrofloxacin eliminated more slowly and accumulated in the cells for a longer time.The confocal microscopy also demonstrated that higher amount of fatty acid SLNs entered the cells with stronger accumulation performance and less amount SLNs absorbed on the cytomembrane as the carbon chain of fatty acids increased. The bactericidal activity of the four fatty acid SLNs against intracellular Salmonella CVCC541 significantly enhanced compared to the free enrofloxacin. These results revealed that fatty acid SLNs, especially docosanoic acid nanoparticles, might be effective nanocarriers to ferry enrofloxacin or other lipid soluble drugs into cells for intracellular bacterial infection treatment.
研究领域:
药剂学
·
微生物学
·
纳米医学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Hongdong Shi,Shuzhang Liu,Junjie Cheng,Siming Yuan,Yang Yang,Tiantian Fang,Kaiming Cao,Kaiju Wei,Qianling Zhang,Yangzhong Liu
Efficient and safe intracellular delivery of proteins is highly desired in the development of protein therapeutics. Current methods of protein delivery commonly suffer from low loading efficiency, low stability in serum, and lack of versatility for different proteins. Here, we developed a platform for efficient protein delivery using mesoporous silica nanoparticles (MSN) with lipid fusion. By different surface modifications on MSN, the positively charged MSN (MSN+) and the negatively charged MSN (MSN–), were generated for loading different proteins. The cargo proteins, based on the surface charges, can be selectively loaded in very high efficiency. The protein-loaded MSNs were fused with liposomes to form a protocell-like delivery system (MSN-LP) in order to prevent burst release of proteins. The lipid fusion significantly increases the stability of the nanosystem in physiological conditions, and the MSN-LP protocell can efficiently deliver proteins into cells. The cargo proteins can be released in cells in a sustained manner. Fifteen different proteins, including two protein complexes, were tested using this delivery system. Further analyses indicate that the proteins can maintain their functions after delivery into cells. Fluorescent proteins, GFP, and KillerRed show fluorescence in cells, indicating the correct folding of proteins during encapsulation and delivery. Protein activity analysis shows that KillerRed protein can generate ROS in cells, while SOD can eliminate ROS in cells. Hence, the proteins delivered by this system remain their structure and function in cells. This work provides a versatile strategy for charge-selective delivery of proteins with high loading efficiency and high stability.
研究领域:
生物医学工程
·
药物递送
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 9
·3172-3179
·
IF 6.6
Wenting Li,Leihou Shao,Ji Liu,Jinhan Sheng,Qizhen Zheng,Ming Wang
Bacterial effector proteins are virulence factors that are secreted and mediate orthogonal post-translational modifications of proteins that are not found naturally in mammalian systems. They hold great promise for developing biotherapeutics by regulating malignant cell signaling in a specific and targeted manner. However, delivering bacterial effectors into disease cells poses a significant challenge to their therapeutic potential. In this study, we report on the design of a combinatorial library of bioreducible lipid nanoparticles containing disulfide bonds for highly efficient bacterial effector delivery and potential cancer therapy. A leading lipid, PPPDA-O16B, identified from the library, can encapsulate and deliver DNA plasmids into cells. The gene cargo is released in response to the reductive cellular environment that is upregulated in cancer cells, leading to enhanced gene delivery and protein expression efficiency. Furthermore, we demonstrate that PPPDA-O16B can deliver the bacterial effector protein, DUF5, to degrade mutant RAS and inactivate downstream MAPK signaling cascades to suppress cancer cell growth in vitro and in tumor-bearing mouse xenografts. This strategy of delivering bacterial effectors using biodegradable lipid nanoparticles can be expanded for cancer cell signaling regulation and antitumor studies.
研究领域:
癌症研究
·
分子生物学
·
纳米医学
·
治疗开发
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Ran Mo,Qiong Sun,Nan Li,Can Zhang
pH-sensitive liposomes (HHG2C 18 -L and PEGHG2C 18 -L) based on zwitterionic oligopeptide lipids as anticancer drug carriers were developed and evaluated for effective intracellular delivery and enhanced antitumor activity . The amino acid-based lipids, 1,5-dioctadecyl- l -glutamyl 2-histidyl-hexahydrobenzoic acid (HHG2C 18 ) and 1,5-distearyl N -( N -α-(4-mPEG2000) butanedione)-histidyl- l -glutamate (PEGHG2C 18 ), were synthesized, which have the multistage pH-response to tumor microenvironmental pH (pH e , pH 6.0–7.0) and endosomal/lysosomal pH (pH i , pH 4.0–6.0) successively. HHG2C 18 -L contains HHG2C 18 , while PEGHG2C 18 -L includes HHG2C 18 and PEGHG2C 18 . Both of them displayed the capability of charge conversion to the surrounding pH. The zeta potentials of HHG2C 18 -L and PEGHG2C 18 -L were negative at pH 7.4, whereas positive at pH 6.5 and more positive at lower pH. Coumarin 6-loaded HHG2C 18 -L (C6/HHG2C 18 -L) and PEGHG2C 18 -L (C6/PEGHG2C 18 -L) showed higher tumor cellular uptake due to electrostatic absorptive endocytosis at pH e (pH 6.5), produced proton sponge effect for endo-lysosomal escape, and accumulated to the mitochondria based on stronger positive charge by the hydrolysis of a pH-sensitive linker at pH i (pH 5.5 and pH 4.5). Furthermore, temsirolimus (CCI-779)-loaded HHG2C 18 -L (CCI-779/HHG2C 18 -L) and PEGHG2C 18 -L (CCI-779/PEGHG2C 18 -L) had significantly higher antiproliferative and apoptosis inducing effects toward the human renal carcinoma (A498) cells at pH 6.5 relative to that at pH 7.4. The half maximal inhibitory concentration (IC50) of CCI-779/HHG2C 18 -L and CCI-779/PEGHG2C 18 -L were about 3 μg/mL and 5 μg/mL at pH 6.5, 1.67-fold and 1.60-fold improved relative to that at pH 7.4, respectively. The total apoptotic ratio of CCI-779/HHG2C 18 -L and CCI-779/PEGHG2C 18 -L increased from 9.90% and 7.78% at pH 7.4 to 19.53% and 12.10% at pH 6.5, respectively. In vivo , CCI-779/PEGHG2C 18 -L after intravenous administration presented remarkably higher bioavailability and blood persistence compared with unPEGylated CCI-779/HHG2C 18 -L, and had the strongest antitumor efficacy against xenograft renal cancer (Renca) tumor models. Accordingly, the results provide the feasibility of using pH-sensitive zwitterionic oligopeptide lipids to extend the applications of liposomes to efficient anticancer drug delivery in cancer therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）