Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Weng Changmei,Li Guanhua,Zhang Dongdong,Duan Zhaoxia,Chen Kuijun,Zhang Jieyuan,Li Tao,Wang Jianmin
Acute lung injury (ALI) has high mortality and still lacks novel and efficient therapies. Zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) are highly expressed in the early stage of ALI and are positively correlated with the progression of pulmonary fibrosis. Herein, we developed a nanoscale Zr(IV)-based porphyrin metal-organic (ZPM) framework to deliver small interfering ZEB1/2 (siZEB1/2) to alleviate early pulmonary fibrosis during ALI. This pH-responsive nano-ZPM system could effectively protect siRNAs during lung delivery until after internalization and rapidly trigger siRNA release under the mildly acidic environment of the endo/lysosome (pH 4.0–6.5) for transfection and gene silencing. Furthermore, the in vivo studies confirmed that this nano-ZPM system could anchor in inflamed lungs. Moreover, the ZEB1/2 silencing led to increased E-cadherin and decreased α-SMA levels. Overall, the nano-ZPM system was an excellent non-viral vector system to deliver siRNAs to alleviate early pulmonary fibrosis during ALI.
研究领域:
药学
·
分子生物学
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纳米技术
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肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-21
·
IF 12.6
Wang Qiuyang,Feng Kai,Wan Guangsheng,Liao Wei,Jin Jing,Wang Peng,Sun Xiaolian,Wang Weijun,Jiang Qing
RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), the most prevalent degenerative joint disease. However, the synergistic effects of these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified Fe3O4 nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs. Subsequently, a poly(vinyl alcohol) (PVA) crosslinked phenylboronic acid (PBA)-modified hyaluronic acid (HA) hydrogel (HPP) was used to encapsulate the si-Fe NPs, resulting in a bifunctional hydrogel (si-Fe-HPP) with reactive oxygen species (ROS)-responsive and RNAi therapeutic properties. Studies in vitro demonstrated that si-Fe-HPP exhibited excellent biocompatibility, anti-inflammatory effects and prolonged stable retention time in knee joint. Intra-articular injection of si-Fe-HPP significantly attenuated cartilage degradation in mice with destabilization of the medial meniscus (DMM)-induced OA. The si-Fe-HPP treatment not only notably alleviated synovitis, osteophyte formation and subchondral bone sclerosis, but also markedly improved physical activity and reduced pain in DMM-induced OA mice. This study reveals that si-Fe-HPP, with its ROS-responsive and RNAi abilities, can significantly protect chondrocytes and attenuate OA progression, providing novel insights and directions for the development of therapeutic materials for OA treatment.Graphical
研究领域:
生物材料
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纳米技术
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骨科
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分子生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Jin Cheng,Shuang Wang,Qianhao Min,Jie Song,Ye Tian
Therapeutic nucleic acid delivery to solid tumors remains a challenge due to enzymatic degradation in cellular uptake and endosomal escape process as well as limited cell permeability. Herein, we reconstructed adoptive-macrophages by integrating functional DNA nanostructure-loaded nucleic acid drugs for tumor immunotherapy. The combination of functional small interfering RNAs (siRNAs) and CpG into DNA tetrahedron (DNA-tet) could induce the repolarization of M2 phenotype macrophages to antitumor M1 type, and releasing proinflammatory cytokines to kill tumor cells. The DNA tet-CpG/siRNA-loaded macrophages show excellent cellular uptake efficiency, parallel delivery capability and induce evident apoptosis and necrosis for tumor cells in vitro. In 4T1 xenograft tumor-bearing mice models, the adoptive macrophage with DNA tet-CpG/siRNA could effectively suppress the growth of subcutaneous tumors persistently and have low side effect for major organs. In summary, our proposed combination therapy of immunological macrophage and DNA-tet-CpG/siRNA will supply new ideas for solid tumor therapy.
研究领域:
癌症治疗
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纳米技术
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免疫治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2018
·
IF 3.408
Bohui Xu,Yan Xu,Gaoxing Su,Hongyan Zhu,Li Zong
Successful delivery of small interfering RNA (siRNA) into the cytoplasm of target cells relies on biocompatible and efficient vectors. In this study, a novel multifunctional core/shell nanoparticle [CS-SS-9R/BSA-c(RGDyK)] was developed to effectively deliver siVEGF to hepatocellular carcinoma cells (Bel-7402 cells). To improve the gene payload and transfection efficiency, a positively charged inner core (CS-SS-9R) was constructed by grafting nona-arginine (9R) onto chitosan (CS) using disulphide bonds. The negatively charged outer shell [BSA-c(RGDyK)] assembled on the surface of the inner core by electrostatic forces that shielded high cationic charges and provided improved targeting. The protein outer shell gradually detached from the inner core in the acidic lysosomal environment, leaving the cationic inner core exposed in order to escape from lysosomes. The nanoparticles were capable of delivering siVEGF into Bel-7402 cells via integrin receptor-mediated endocytosis. Successful lysosomal escape of the inner core and the rapid release of siVEGF into the cytoplasm resulted in a 78.9% decrease in VEGF expression and 81.2% inhibition of tumour cell proliferation. In conclusion, this nanoparticle is responsive to the intracellular environment and accurately delivered siRNA into the cytoplasm, providing a safe and highly efficient gene delivery strategy for cancer therapy.
研究领域:
纳米技术
·
癌症生物学
·
药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Jie Ding,Tingxizi Liang,Qianhao Min,Liping Jiang,Jun-Jie Zhu
For codelivery of therapeutic genes and chemical agents in combined therapy, the ideal drug delivery system entails high-capacity and low-body toxicity carriers, allowing adequate drug dose for tumor regions while yielding low residues in normal tissues. To augment the gene/drug load capacity and circumvent the potential toxicity brought by traditional inorganic and polymeric nanocarriers, a “stealth” carrier was herein designed in a simple self-assembly of (−)-epigallocatechin-3-O-gallate (EGCG) and small interfering RNA (siRNA) by recruiting protamine as a biodegradable medium for the treatment of drug-resistant triple-negative breast cancer. In the self-assembled nanogel, entrapped siRNA played a central role in sensitizing the tumor response to EGCG-involved chemotherapy, and the positively charged protamine served as the assembly skeleton to fully accommodate gene and drug molecules and minimize the factors causing side effects. As compared to stand-alone chemotherapy with EGCG, the multicomponent nanogel revealed a 15-fold increase in the cytotoxicity to drug-resistant MDA-MB-231 cell line. Moreover, equipped with hyaluronic acid and tumor-homing cell-penetrating peptide as the outmost targeting ligands, the siRNA- and EGCG-loaded nanogel demonstrates superior selectivity and tumor growth inhibition to free EGCG in xenograft MDA-MB-231 tumor-bearing mice. Meanwhile, thanks to the acknowledged biosafety of protamine, little toxicity was found to normal tissues and organs in the animal model. This gene/drug self-assembly caged in a biodegradable carrier opens up an effective and secure route for drug-resistant cancer therapy and provides a versatile approach for codelivery of other genes and drugs for different medical purposes.
研究领域:
癌症治疗
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纳米技术
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药学
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 73
·期 8
·1128-1135
·
IF 3.765
Li Guo,Meng Fayan,Lu Taicheng,Wei Liying,Pan Xin,Nong Zhenzhen,Wei Mei,Liao Chuanan,Li Xuehua
ObjectiveMolybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.MethodsMoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed.Key findingsThe nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone.ConclusionsOur results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Aili Suo,Junmin Qian,Minghui Xu,Weijun Xu,Yaping Zhang,Yu Yao
Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanovehicle has emerged as a promising combination therapy approach to treating cancers because of their synergistic effect. Nanocarrier delivery systems with low cytotoxicity and high efficiency are needed for such a purpose. In this study, a novel folate-conjugated PEGylated cationic triblock copolymer, poly(acrylhydrazine)- block -poly(3-dimethylaminopropyl methacrylamide)- block -poly(acrylhydrazine) (PAH- b -PDMAPMA- b -PAH), was synthesized and evaluated as a stimuli-sensitive vehicle for the targeted co-delivery of doxorubicin (DOX) and Bcl-2 siRNA into breast cancer MCF-7 cells. The synthetic process of the PEGylated triblock copolymer involved sequential reversible addition-fragmentation chain transfer polymerization, PEGylation and removal of tert -butoxy carbamate protecting groups. Folate-conjugated and/or -unconjugated poly(ethylene glycol) segments were grafted onto PAH- b -PDMAPMA- b -PAH via a reduction-sensitive disulfide linkage. The synthetic polymers were characterized by 1 H NMR and gel permeation chromatography. The PEGylated triblock copolymer could chemically conjugate DOX onto PAH blocks via pH-responsive hydrazone bonds and simultaneously complex negatively charged Bcl-2 siRNA with cationic PDMAPMA blocks through electrostatic interactions at N/P ratios ≥ 32:1 to form multifunctional nanomicelleplexes. The nanomicelleplexes exhibited spherical shape, possessed a positively charged surface with a zeta potential of + 22.5 mV and had a desirable and uniform particle size of 187 nm. In vitro release studies revealed that the nanomicelleplexes could release DOX and Bcl-2 siRNA in a reduction and pH dual-sensitive manner and the payload release was significantly enhanced in a reductive acidic environment mimicking the endosomes/lysosomes of cancer cells compared to under physiology conditions. Furthermore, the release of both DOX and siRNA was found to follow Higuchi kinetic model. Confocal laser scanning microscopy, flow cytometry and MTT analyses confirmed that, compared with folate-undecorated nanomicelleplexes, folate-decorated nanomicelleplexes could more effectively co-deliver DOX and Bcl-2 siRNA into MCF-7 cells and showed a stronger cell-killing effect. The pristine PEGylated triblock copolymer exhibited good cytocompatibility. Moreover, co-delivery of DOX and Bcl-2 siRNA achieved a significant synergistic antitumor efficacy. These findings suggested that the folate-decorated PEGylated cationic triblock copolymer might be a promising vehicle for targeted intracellular co-delivery of DOX and siRNA in MCF-7 cells, representing a potential clinical combination therapy for breast cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Zhenjiang Zheng,Dingchuan Peng,Mengfei Li,Xuehan Lu,Songlin Gong,Yuan Yuan,Epiphane K. Silli,Jiali Tang,Qiaoyun Zhao,HaoYun Xu,Yufei Lan,Chunlu Tan,Ying Wang
Due to the malignant proliferation and severe tumor fibrosis of pancreatic cancer (PC), the efficacy of chemotherapy has been largely limited. Peptidyl-prolyl cis -trans isomerase NIMA-interacting 1 (Pin1) promotes tumor progression by promoting collagen synthesis and tumor cell proliferation . In this study, we developed nano-liposomes (FU-GEM/Pin1 siRNA@LIP) that act simultaneously on pancreatic tumor cells. FU-GEM/Pin1 siRNA@LIP were designed with suitable particle size and potential, and effectively loaded with Pin1 siRNA and fucoidan (FU) while demonstrating good release stability and biocompatibility . Our study showed that FU-GEM/Pin1 siRNA@LIP effectively inhibited the proliferation of Panc01 and Panc02 tumor cells and significantly enhanced the uptake of these two types of cells in vitro . FU-GEM/Pin1 siRNA@LIP might cause tumor damage, promote apoptosis and reduce collagen formation in vivo . Molecular and histological studies demonstrated that FU-GEM/Pin1 siRNA@LIP regulated the expression of CDH11 and α-SMA, and also reducing collagen synthesis of peripheral matrix. In summary, our experiments highlight that FU-GEM/Pin1 siRNA@LIP is an effective combination delivery system. It can inhibit tumor cell proliferation in vitro , promote tumor cell apoptosis and reduce collagen synthesis in vivo . This system could provide a promising therapeutic option for PC.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 44
·7756-7764
·
IF 0
Jiang Wu,Ying Liu,Wei Li,Chunyan Wang,Yanjun Li,Ying Tian,Jing Sun,Shouju Wang,Xin Wang,Yuxia Tang,Hong Zhu,Zhaogang Teng,Guangming Lu
Small interfering RNA (siRNA) has great potential for gene therapy of breast cancer. The development of multifunctional nanocarriers possessing the targeted ability and multimodal imaging function is important to increase siRNA transfection efficiency and to visualize the delivery events. Herein, we demonstrate flavin mononucleotide (FMN) and polyethylenimine (PEI) modified Fe3O4@mTiO2 nanoparticles (Fe3O4@mTiO2/FMN-PEI) as novel magnetic fluorescent siRNA delivery systems. The system has magnetic targeting, magnetic resonance imaging (MRI), optical imaging, and high siRNA binding ability. Survivin-siRNA delivered by this system can effectively enter into MCF-7 cells, which can be further enhanced by exerting an external magnetic field. More importantly, the siRNA delivery events including the location, trafficking, distribution, and release, can be visualized by MRI and optical imaging. Gene silencing by survivin-siRNA can cause significant protein knockdown (96%) and considerable cell apoptosis (30%), indicating the usefulness of Fe3O4@mTiO2/FMN-PEI as a siRNA delivery system.
研究领域:
癌症研究
·
基因治疗
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纳米技术
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生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Jiaojiao Zhu,Man Guo,Yanhui Cui,Yingcai Meng,Jinsong Ding,Wenbin Zeng,Wenhu Zhou
Pulmonary delivery of anti-inflammatory siRNA presents a promising approach for localized therapy of acute lung injury (ALI), while polycationic vectors can be easily trapped by the negatively charged airway mucin glycoproteins and arbitrarily internalized by epithelial cells with nontargetability for immunological clearance. Herein, we report a material, the dopamine (DA)-grafted hyaluronic acid (HA–DA), coating on an anti-TNF-α vector to address these limitations. HA–DA was simply synthesized and facilely coated on poly(β-amino ester) (BP)-based siRNA vectors via electrostatic attraction. The resulting HA–DA/BP/siRNA displayed significantly enhanced mucus penetration, attributable to the charge screen effect of HA–DA and the bioadhesive nature of the grafting DA. After transmucosal delivery, the nanosystem could target diseased macrophages via CD44-mediated internalization and rapidly escape from endo/lysosomes through the proton sponge effect, resulting in effective TNF-α regulation. Meanwhile, DA modification endowed the coating material with robust antioxidative capability to scavenge a broad spectrum of reactive oxygen/nitrogen species (RONS), which protected the lung tissue from oxidative damage and synergized with anti-TNF-α to inhibit a cytokine storm. As a result, a remarkable amelioration of ALI was achieved in a lipopolysaccharide (LPS)-stimulated mice model. This study provides a multifunctional coating material to facilitate pulmonary drug delivery for the treatment of lung diseases.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
肺科学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Kaili Wang,Hao Chen,Si Qin,Shuhui Chen,Qian Zhang,Jiali Chen,Donghua Di,Guangyue Su,Yue Yuan
Hepatic fibrosis, as a destructive liver disease, occurs due to activated hepatic stellate cells (HSCs) producing excessive extracellular matrix deposition. If left untreated, it could further deteriorate into cirrhosis and hepatoma with high morbidity and mortality. Currently, to break the dilemma of poor targeting efficiency on HSCs and limited effect of monotherapy, it is urgent to explore a precise and efficient treatment against liver fibrosis. In the present work, a novel multifunctional nanoplatform based on vitamin A (VA) modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was designed for co-delivery of chemical drug (Pirfenidone) and genetic drug (TGF-β 1 siRNA) to achieve HSCs targeting mediated synergistic chemo-gene therapy against liver fibrosis. With the large specific surface area and acid-responsive degradation characteristics, ZIF-8 nanoparticles have great advantages to achieve high loading efficiency of Pirfenidone and enable acid-reactive drug release. After complexing siRNA, the prepared chemo-gene drug co-delivered nanocomplex (GP@ZIF-VL) proved excellent serum stability and effectively protected siRNA from degradation. Importantly, in vitro cell uptake and in vivo biodistribution demonstrated that VA functionalization markedly enhanced the delivery efficiency of GP@ZIF-VL nanocomplex into HSCs. As expected, GP@ZIF-VL significantly reduced extracellular matrix deposition and ameliorated hepatic fibrosis, as evidenced by decreased levels of liver enzymes in serum and a reduction in the hydroxyproline content in liver tissue. Therefore, GP@ZIF-VL nanocomplex displayed a bright future on the treatment of liver fibrosis with HSCs-targeting mediated chemo-gene synergetic therapy.
研究领域:
药学
·
纳米技术
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分子生物学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao
Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.
研究领域:
药学
·
免疫学
·
癌症研究
·
纳米技术
✓ 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）