Frontiers in Pharmacology
·
2022
·
IF 5.988
Xi Chen,Di Wang,Xuejun Guo,Xiaoming Li,Wenjing Ye,Yang Qi,Wen Gu
The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin's effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
研究领域:
药理学
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纳米技术
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 99
·97096-97106
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IF 3.289
Ning Cui,Junmin Qian,Jinlei Wang,Yaping Wang,Weijun Xu,Hongjie Wang
Polypeptides synthesized from α-amino acid N-carboxyanhydrides are considered ideal candidates as scaffold materials for bone tissue engineering due to their excellent biocompatibility and non-toxic degradation products. However, undesirable mechanical properties and osteoinductivity restrict their application in bone healing and regeneration. To overcome these limitations, we modified a synthetic polypeptide poly(Nε-Cbz-L-lysine) (PZL) with poly(lactic-co-glycolic acid) (PLGA) having relatively high strength and osteoinductive bioglass (BG) particles, and fabricated foamy PZL/PLGA/BG composite scaffolds using a negative NaCl-templating method. The morphology, compression modulus, thermal and degradation behaviors of the PZL/PLGA/BG composite scaffolds were characterized, and the in vitro biocompatibility was evaluated with MC3T3-E1 cells using live/dead staining, MTT and ALP assays. The results indicated that the PZL/PLGA/BG composite scaffold with a weight ratio of 5 : 5 : 1 (PZL5PLGA5BG) had higher compression modulus and protein adsorption and mineralization abilities than other scaffolds, and was more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells. The in vivo biocompatibility of the scaffolds was evaluated in both rat subcutaneous model and rabbit tibia defect model. The results of histological studies of subcutaneous implants, as confirmed by H&E, Masson's trichrome and CD34 staining assays, demonstrated that the PZL5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels and exhibited reduced inflammation response as compared to other scaffolds after 8 weeks of implantation. In experimental studies in bone defect model, the results of digital radiography and H&E staining confirmed that the PZL5PLGA5BG composite scaffolds after 8 weeks of implantation significantly improved in vivo osteogenesis. The newly formed bone tissue grew into the scaffolds along with the degradation of the materials. To sum up, the foamy PZL/PLGA/BG composite scaffolds had good comprehensive performances and would meet the needs of bone regeneration.
研究领域:
生物医学工程
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材料科学
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组织工程
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生物材料
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产品关联
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
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IF 9.078
Yu Chen,Long Chen,Yitong Wang,Kaili Lin,Jiaqiang Liu
The repair of bone defects in patients with diabetes mellitus (DM) is a challenge in clinical treatment mainly because of inhibited osteogenesis caused by stem cell dysfunction. Our research found that high glucose induced the activation of GSK-3β, which played an important role in this process. Inhibited GSK-3β induced an acceptable osteogenic effect of lithium ions . However, whether lithium-containing biomaterials can exert a good bone-repair effect under the pathological state of DM is still unclear. Therefore, we synthesized a type of lithium-containing mesoporous bioactive glasses (Li-MBG), and explored their in vitro roles in regulating the proliferation, migration and osteogenic differentiation of BMSCs under the high-glucose microenvironment , and the underlying mechanism. Meanwhile, Li-MBG/PLGA composite scaffolds were prepared by 3D printing , followed by investigating their in vivo effects on repairing critical skull defects of DM mice. We found that Li-MBG reversed high glucose-induced suppression in the proliferation, migration and osteogenic differentiation of BMSCs by upregulating Itga3 and activating the β-catenin/Tcf7/Ccn4 signaling pathway. Li-MBG/PLGA composite scaffolds could effectively repair skull defects of DM mice by recruiting stem cells, presenting an excellent osteogenesis effect. Our findings provide references for clinical bone defect repair in DM patients.
研究领域:
生物材料
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组织工程
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糖尿病研究
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骨再生
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产品关联
DOI
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Cai Chenlei,Xie Yuexia,Wu liangliang,Chen Xiaojing,Liu Hongmei,Zhou Yan,Zou Hanbing,Liu Dejun,Zhao Yanan,Kong Xianming,Liu Peifeng
Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide- co -glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo , to inhibit HCC progression. In vitro , PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent Lipofectamine TM 2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo , miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.
研究领域:
癌症研究
·
分子生物学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Zhichao Hu,Jiaqi Lu,Annan Hu,Yongjiang Dou,Sheng Wang,Dihan Su,Wang Ding,Ruixian Lian,Shunyi Lu,Lan Xiao,Yu-Lin Li,Jian Dong,Jian Zhou,Xuyong Yang,Libo Jiang
Bone regeneration following the removal of tumor tissues remains a major clinical challenge for the treatment of bone defects, in which materials with combinatory bone repair and osteolytic metastasis therapy is considered as a promising solution. Herein, a highly strong delignified wood/regenerated silk fibroin (RSF) hydrogel scaffold integrated with black phosphorus quantum dots (BPQDs) encapsulated by poly (lactic-co-glycolic acid) (PLGA) was engineered to realize efficient mechanical supporting, bone regeneration, and tumor therapy. Following delignification, the white wood (WW) scaffold significantly improved the mechanical properties of RSF composite hydrogel, with the elastic modulus in the L-direction and R-direction of 300 MPa and 3.3 MPa, and compression modulus in the L-direction of 9.3 MPa. Moreover, the WW/RSF hydrogel scaffold with BPQD/PLGA nanospheres effectively promoted the proliferation, migration, and osteogenic differentiation of bone mesenchymal stem cells and enhanced osteogenesis in vivo . Compared with the vertical implantation method, better bone regeneration was observed in parallel implantation system parallel to bone shaft. Importantly, the BPQDs in the hydrogel scaffolds could inhibit osteoclast differentiation and exhibit photothermal effects against metastatic tumor in the spine. Our data provide promising evidence for the potential therapeutic application on bone regeneration and ablation of bone metastasis.
研究领域:
生物医学工程
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材料科学
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组织工程
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癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yunhai Wei,Wenjing Hu,Huancen Guo,Jinyu Zhang,Jingrui Cao,Chu Shen,Zhongxin Wu,Lei Yin,Yuhai Gao
Immune checkpoint inhibitors (ICIs) show effectiveness in gastric cancer (GC) treatment, yet enhancing their efficacy remains challenging. We encapsulated the anticancer compound Heterophyllin B (HB) in mPEG–PLGA-NH2 nanoparticles (NPs), modified with αPDL1, forming mPEG–PLGA-NH2@HB-αPDL1 NPs. These NPs displayed low toxicity to GES-1 cells and good blood compatibility. They effectively inhibited GC cell malignant phenotypes and downregulated PD-L1 expression via the PI3K/AKT pathway. In GC allograft mice, the HB and αPDL1 combination therapy outperformed monotherapy, with the NPs showing better efficacy than free drugs. Additionally, the NPs improved the tumor immune microenvironment. H&E staining confirmed no significant toxicity to major mouse organs. Thus, mPEG–PLGA-NH2@HB-αPDL1 offers a promising strategy for optimizing ICI therapy in GC treatment.
研究领域:
纳米医学
·
肿瘤学
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免疫治疗
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
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IF 6.044
Ping Liu,Nana Chen,Lei Yan,Fei Gao,Dongsheng Ji,Shijiao Zhang,Litao Zhang,Yuqin Li,Yuliang Xiao
The purpose of this study was to ascertain the effect of chondroitin sulphate-modified doxorubicin (Dox) nanoparticles on enhancing the tumour-targeting effect and tumour growth inhibition effect of doxorubicin both in vitro and in vivo . The chondroitin sulphate-doxorubicin conjugate and its poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CS-Dox-PLGA) were successfully synthesised, and then characterized by Fourier-transform infrared spectroscopy (FTIR), proton magnetic resonance ( 1 HNMR), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), transmission electron microscope (TEM), zeta potential and laser light scattering. Taking advantage of the enhanced permeability and CD44-mediated endocytosis, CS-Dox-PLGA showed excellent capacity for penetrating the peripheral tumour barrier and into the nucleus of tumour cells. The CS-Dox-PLGA cellular uptake was improved and exhibited a significantly higher level of cytotoxicity in U251 cells. After intravenous administration, the CS-Dox-PLGA showed good pharmacokinetic properties and excellent U251-induced tumour inhibition with low cardiac toxicity. Therefore, CS-Dox-PLGA with low cardiac toxicity and good anti-tumour ability might be a better choice for Dox in clinical practice.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Jia Zhou,Zhaohui Jiang,Runbin Sun,Di Pan,Qianming Du,Xiang Zhou,Yi Chen,Yan Chen,Jianqing Peng
Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2013
·
IF 2.404
Junmin Qian,Weijun Xu,Xueqing Yong,Xinxia Jin,Wei Zhang
In this study, biomorphic poly( dl -lactic- co -glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164 ± 52 μm and 13 ± 8 μm, respectively, with a porosity of 89.3 ± 1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400 μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering.
研究领域:
生物材料
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组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2025
·
IF 2.8
Gang Chen,Hai Lan
To address the issues of collapse-type degradation and poor toughness observed in PLGA-based bone repair scaffolds during degradation, this study blends PLGA with poly (trimethylene carbonate) (PTMC) and fabricates microsphere scaffolds through the emulsion method followed by sintering to form solid microsphere scaffolds. Additionally, to enhance the osteogenic potential of the scaffold, β-tricalcium phosphate (β-TCP) and varying amounts of titanium dioxide (TiO 2 ) are incorporated into the polymer. Performance analysis of the composite microsphere scaffolds reveals that the scaffold exhibits a continuous pore structure with a compressive modulus comparable to that of cancellous bone. After the incorporation of inorganic particles, the compressive modulus exceeded 70 MPa. In vitro degradation experiments confirm that the composite microsphere scaffold prepared by blending PTMC exhibited a degradation rate of 9.1% at week 12 while maintaining stable macroscopic morphology. Moreover, the pH at the final stage of degradation effectively mitigated the issue of acidic degradation associated with PLGA (pH = 6.32). In vitro cell experiments demonstrate that the prepared microsphere scaffolds possess good biocompatibility, and the incorporation of β-TCP and TiO 2 enhances the composite scaffold's osteogenic potential and antibacterial properties. This scaffold holds promise as a novel approach for the treatment of bone defects.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
高分子科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
VETERINARY RESEARCH
·
2022
·Vol. 53
·期 1
·1-21
·
IF 3.829
Yu ZhengQing,Chen SiYing,Huang JianMei,Ding WenXi,Chen YuFeng,Su JunZhi,Yan RuoFeng,Xu LiXin,Song XiaoKai,Li XiangRui
With a worldwide distribution, Eimeria spp. could result in serious economic losses to the poultry industry. Due to drug resistance and residues, there are no ideal drugs and vaccines against Eimeria spp. in food animals. In the current study, a bioinformatics approach was employed to design a multiepitope antigen, named NSLC protein, encoding antigenic epitopes of E. necatrix NA4, E. tenella SAG1, E. acervulina LDH, and E. maxima CDPK. Thereafter, the protective immunity of NSLC protein along with five adjuvants and two nanospheres in laying chickens was evaluated. Based on the humoral immunity, cellular immunity, oocyst burden, and the coefficient of growth, the optimum adjuvant was evaluated. Furthermore, the optimum immune route and dosage were also investigated according to the oocyst burden and coefficient of growth. Accompanied by promoted secretion of antibodies and enhanced CD4+ and CD8+ T lymphocyte proportions, NSLC proteins entrapped in PLGA nanospheres were more effective in stimulating protective immunity than other adjuvants or nanospheres, indicating that PLGA nanospheres were the optimum adjuvant for NSLC protein. In addition, a significantly inhibited oocyst burden and growth coefficient promotion were also observed in animals vaccinated with NSLC proteins entrapped in PLGA nanospheres, indicating that the optimum adjuvant for NSLC proteins was PLGA nanospheres. The results also suggested that the intramucosal route with PLGA nanospheres containing 300 μg of NSLC protein was the most efficient approach to induce protective immunity against the four Eimeria species. Collectively, PLGA nanospheres loaded with NSLC antigens are potential vaccine candidates against avian coccidiosis.
研究领域:
兽医学
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免疫学
·
纳米技术
·
家禽健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Yinghua Tao,Xin Tan,Tianzhu Zhang
Non-degradable polymers, when retained in the body for long periods, can cause chronic inflammation and immune responses. This issue increases the costs related to secondary surgeries and overall healthcare. Conversely, while biodegradable polymers such as PLGA offer an alternative, their degradation rate is challenging to precisely control. Additionally, their mechanical properties deteriorate during the degradation process, and the degradation by-products may lead to localized acidification or other adverse reactions. In this study, we introduce a new biodegradable copolymer called 4arm-PLGA-Amino acid (4aPLGA-Amino acid). This copolymer is synthesized by grafting amino acids onto 4arm-PLGA (4aPLGA) using triphosgene, which is both environmentally friendly and cost-effective. The incorporation of amino acids aims to enhance the biocompatibility and functionality of the copolymer. By varying the types of amino acids grafted, the degradation rate of 4aPLGA can be modulated, thereby improving its potential for applications in drug delivery systems. This modification also promotes cell attachment and proliferation, making it suitable for tissue engineering and regenerative medicine. The study demonstrated that 4aPLGA-Amino acid significantly improved biocompatibility, degradation control, and mechanical properties, broadening its applicability in various biomedical engineering fields.
研究领域:
生物医学工程
·
材料科学
·
药学
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子