RSC Advances
·
2018
·Vol. 8
·期 48
·27191-27200
·
IF 2.936
Qinli Xu,Ye Li,Yuhang Zhu,Kunchi Zhao,Rui Gu,Qingsan Zhu
Poly(lactic-co-glycolic acid) (PLGA) and hydroxyapatite (HA) are considered potential osteoinductive materials because of their biodegradability and mineralization features. However, the hydrophobicity of scaffold surfaces is less supportive of cell attachment and proliferation because of poor wettability. The mode of binding of growth factors to the scaffold also affects cell differentiation into osteoblasts. The half-life of a growth factor in vivo can be increased by binding the factor to the scaffold surface. In this work, we prepared a porous PLGA/HA scaffold grafted with recombinant human bone morphogenic protein-7 (rhBMP-7) attached via polydopamine (pDA) for bone repair. The pDA coated PLGA/HA (pDA-PLGA/HA) scaffolds were characterized by energy dispersive X-ray analysis and Fourier-transform infrared spectroscopy. The microstructure and porosity of PLGA/HA scaffolds were analyzed by scanning electron microscopy and micro-computed tomography. The release profile of rhBMP-7 grafted onto the pDA-PLGA/HA (pDA-PLGA/HA/BMP-7) scaffolds was examined for 21 days. The attachment efficiency, cell proliferation rate, alkaline phosphatase activity, calcium deposition, and osteoblast-related gene expression of bone marrow-derived stem cells to PLGA/HA, pDA-PLGA/HA, and pDA-PLGA/HA/BMP-7 scaffolds were evaluated. To assess the ability of bone repair in vivo, scaffolds were implanted into critical-sized calvarial defects created in mice, and the in vivo tissue-engineered bone was monitored by micro-computed tomography and histology. In vivo experiments revealed rapid healing of the defects treated with the pDA-PLGA/HA/BMP-7 scaffolds compared with pDA-PLGA/HA and PLGA/HA scaffolds at week 8 post-surgery. These results collectively demonstrate that the rhBMP-7-immobilized PLGA/HA scaffold via pDA is a promising candidate for calvarial repair.
研究领域:
生物医学工程
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组织工程
·
材料科学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 8
·2400045
·
IF 3.7
Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi
Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.
研究领域:
肿瘤学
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纳米技术
·
药理学
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细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Fanjun Zhang,Yao Xiong,Yage Hu,Jingze Liu,Yuan Wei,Li Yang,Rifang Luo,Yunbing Wang
The endothelial glycocalyx is a natural protective layer for blood vessels. Efficient construction of a reliable glycocalyx-mimetic coating on a vascular implant possesses great potential but remains a challenge. Herein, a novel glycocalyx-mimetic coating featuring the clustered morphology and hydrophilic lubrication is developed via the layer-by-layer self-assembly of polyethyleneimine (PEI) and phosphorylcholine-modified hyaluronic acid (HA-PC). The zwitterionic PC groups in HA-PC exhibited an anti-polyelectrolyte effect to induce the molecular folding and aggregation of HA in solution and enhance its binding capacity to PEI, resulting in an endothelial glycocalyx-mimetic clustered morphology. Besides, zwitterions, rather than hydrophobic groups, can achieve hydrophilic lubrication properties through spatial synergy with HA while inducing the molecular folding of HA, ultimately constructing a glycocalyx-mimetic coating. Such a coating can function well as armor to vascular stent, by virtue of excellent anti-coagulation, anti-inflammation, and endothelial promotion properties in vivo and in vitro. The findings not only provide new insights into the interactions between PC-modified polyelectrolytes but also render a promising glycocalyx-mimetic coating to armor vascular implants.
研究领域:
生物材料
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组织工程
·
生物医学工程
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血管生物学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 9
·3453-3464
·
IF 6.843
Xiaofang Li,Wen Zhang,Jing Lin,Hao Wu,Yucen Yao,Jiayi Zhang,Chunrong Yang
The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment-responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)-disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) “antibody” to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a “membrane escape effect” and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.
研究领域:
肿瘤学
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药理学
·
免疫疗法
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Guiqiao Wang,Weiye Shi,Defang Ma,Baoyu Gao
Bisulfite-activated permanganate (PM/BS) oxidation process can oxidize ciprofloxacin in complex water matrices rapidly. However, effects of PM/BS pre-oxidation on the formation of disinfection byproducts (DBPs) during post-chlorination of ciprofloxacin-contaminated waters need to be addressed. This study investigated the formation of trihalomethanes (THMs), haloacetonitriles (HANs), haloketones and trichloronitromethane during chlorination of ciprofloxacin-contaminated humic acid (HA), bovine serum albumin (BSA) and alginate solutions, and revealed the effects of PM/BS pre-oxidation on ciprofloxacin degradation and DBP formation during post-chlorination, considering the presence of Br − . Only THMs and HANs were quantifiable. THMs were the most abundant. Ciprofloxacin-contaminated HA exhibited the highest formation potential of DBPs and integrated toxic risk value (ITRV). In the absence of Br − , PM/BS pre-oxidation reduced or hardly affected the toxicity risks derived from DBPs formed from the post-chlorination. However, the presence of Br − greatly reduced the degradation of ciprofloxacin (30–50%) in various waters. In the ciprofloxacin-contaminated waters containing Br − , the total ITRVs of DBPs formed from post-chlorination increased by 60%–800% with PM/BS pre-oxidation, attributing to the enhanced formation of DBPs especially bromochloroacetonitrile and dibromoacetonitrile. Overall, PM/BS is a potential pre-oxidation technology for the treatment of ciprofloxacin-contaminated waters without bromide.
研究领域:
环境科学
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水处理
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化学工程
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 42
·20030-20044
·
IF 6.97
Lin Hou,Dandan Chen,Lisha Hao,Chunyu Tian,Yingshan Yan,Ling Zhu,Huijuan Zhang,Yi Zhang,Zhenzhong Zhang
Cancer-associated fibroblasts (CAFs) are important barriers for nanoparticles (NPs) to deeply penetrate into tumors and severely limit the antitumor efficacy of nanomedicines. Herein, we proposed a CAF-triggered transformable drug delivery system based on a cleavable peptide responsive to fibroblast activation protein-α (FAP-α) specifically overexpressed on the surface of CAFs. The NPs were composed of cationic poly(amidoamine) (PAMAM) dendrimers cross-linked by our designed peptide, a chemotherapeutical drug was incorporated onto PAMAM using disulfide bonds and finally, hyaluronic acid (HA) was conjugated to improve the tumor targetability as well as biocompatibility through electrostatic interactions. These NPs had an initial size of ∼200 nm and negative zeta potential favorable for stable blood circulation; however, after docking with CAFs, they dissociated into smaller NPs and exposed the relative positive surface charge to facilitate penetration and enter the tumor cells together with CAFs. An interesting finding was that this system intracellularly released different levels of drugs in these two kinds of cells, which was beneficial for the disruption of the stromal barrier and increasing the local drug accumulation. Our investigation confirmed that the constructed system could alleviate the biological barriers and hold promising therapeutic efficiency for desmoplastic solid tumors.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Wenbo Zhang,Pu Xu,Yanan Cheng,Yanlan Yang,Qiuhua Mao,Zuogeng Chen
A nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material was prepared, and its biological properties were evaluated. The nanopearl powder/C-HA/rhBMP-2 composite porous artificial bone material was prepared using the freeze-drying method after the nanopearl powder was prepared using mechanical ball milling. The particle was measured with a transmission electron microscope, its surface morphology and pore size were observed under a scanning electron microscope. The porosity of the artificial bone was determined using pycnometry, a compression performance test was conducted with a universal testing machine, and XRD (X-ray diffraction) patterns were recorded to examine the crystal form of the pearl powder in the composite artificial bone. Finally, the artificial bone was cocultured with mouse MC3T3-E1 cells to investigate its effects on cell proliferation and differentiation and the expression of osteogenesis-related genes. The pearl powder prepared in this experiment had a particle size in the nanometer range. This nanopearl powder, along with C-HA and rhBMP-2, was compounded into the nanopearl powder/C-HA/rhBMP-2 composite artificial bone, showing pore sizes of 188.53 ± 15.32 μm, a porosity of 86.43 ± 2.78% and a compressive strength of 0.342 ± 0.024 MPa. Notably, rhBMP-2 was released from the artificial bone in a sustained manner. Moreover, this artificial bone promoted the adhesion, proliferation, and differentiation of MC3T3-E1 cells and upregulated the expression of ColαI (collagen α1), OCN (osteocalcin), OPN (osteopontin) and Runx2 (runt-related gene 2). Conclusively, this nanopearl powder/C-HA/rhBMP-2 composite artificial bone material showed good performance and cytocompatibility, suggesting that it can be used for bone tissue engineering.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Mengyun Peng,Hongyan Dong,Meiyu Shao,Xiaoqing Zhang,Jiamei Sun,Chuan Ding,Xin Han,Qiao Yang,Xianan Sang,Gang Cao
Hepatocellular carcinoma (HCC) is an immunosuppressive tumor associated with high mortality. Photothermal and photodynamic therapies have been applied to induce immunogenic cell death (ICD) in HCC, successfully eliciting immune responses but facing limitations in penetration depth in clinical trials . Here, intrinsic mitochondrial hyperthermia was used to trigger thermosensitive drug release. The mitochondria were further self-heated through 2,4-dinitrophenol uncoupling, dramatically promoting free radical initiation and inducing tumor ICD. The synthesized mitochondrial-targeting TPP-HA-TDV nanoparticles specifically generated free radicals in the mitochondria without external stimulation, and obviously enhanced the release of ICD markers, subsequently evoking immune responses. The results showed that mitochondrial hyperthermia could be an endogenous target for thermosensitive drug release. Furthermore, self-heating mitochondria-induced free radical blast could be an efficient therapeutic for deep-seated tumor therapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Yufeng Guo,Haixing Xu,Yiping Li,Fengzheng Wu,Yixuan Li,Yun Bao,Xiumei Yan,Zhijun Huang,Peihu Xu
Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Kaili Wang,Hao Chen,Jiani Zheng,Jiali Chen,Yixuan Chen,Yue Yuan
Dual pathological barriers, including capillarized liver sinusoidal endothelial cells (LSECs) and deposited extracellular matrix (ECM), result in insufficient drug delivery, significantly compromising the anti-fibrosis efficacy. Additionally, excessive reactive oxygen species (ROS) in the hepatic microenvironment are crucial factors contributing to the progression of liver fibrosis. Hence, hyaluronic acid (HA) modified liposomes co-delivering all-trans retinoic acid (RA) and L-arginine (L-arg) were constructed to reverse hepatic fibrosis. By exhibiting exceptional responsiveness to the fibrotic microenvironment, our cleverly constructed liposomes efficiently disrupted the hepatic sinus pathological barrier, leading to enhanced accumulation of liposomes in activated hepatic stellate cells (HSCs) and subsequent induction of HSCs quiescence. Specially, excessive ROS in liver fibrosis promotes the conversion of loaded L-arg to nitric oxide (NO). The ensuing NO serves to reestablish the fenestrae structure of capillarized LSECs, thereby augmenting the likelihood of liposomes reaching the hepatic sinus space. Furthermore, subsequent oxidation of NO by ROS into peroxynitrite activates pro-matrix metalloproteinases into matrix metalloproteinases, which further disrupts the deposited ECM barrier. Consequently, this NO-induced cascade process greatly amplifies the accumulation of liposomes within activated HSCs. More importantly, the released RA could induce quiescence of activated HSCs by significantly downregulating the expression of myosin light chain-2, thereby effectively mitigating excessive collagen synthesis and ultimately leading to the reversal of liver fibrosis. Overall, this integrated systemic strategy has taken a significant step forward in advancing the treatment of liver fibrosis.
研究领域:
药理学
·
肝病学
·
药物递送系统
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Haoyu Chen,Minjuan Wang,Qiquan Yang,Jing Liu,Feng Liu,Xiaohua Zhu,Shu Huang,Peng Yin,Xingfeng Wang,Haitao Li,Youyu Zhang,Meiling Liu,Mingjie Wei,Shouzhuo Yao,Yang Liu
The integration of reactive oxygen species (ROS) related photodynamic therapy (PDT) with the strategy of reshaping the tumor microenvironment (TME) has emerged as a potential approach for nanodiagnostic and therapeutic interventions. However, the therapeutic efficacy based on ROS treatments may be hindered by intracellular antioxidants such as glutathione (GSH) and tumor hypoxia. To address these challenges, a nanoplatform based on GSH-responsive multifunctional porphyrinic metal–organic framework (PCN-224@Au@MnO 2 @HA, PAMH) was proposed. It was developed through a layer-by-layer in-situ growth method. This method avoids the need for high-temperature calcination and complex modification processes while improving the stability of PCN-224 in a phosphate-rich environment. GSH depletion leads to oxidation–reduction imbalance in TME. With the inactivation of GSH peroxidase 4 (GPX4), the content of hydrogen peroxide (H 2 O 2 ) increases, ultimately triggering lipid peroxidation (LPO) and promoting ferroptosis. The catalase-like activity of Au nanozymes facilitates the generation of oxygen (O 2 ), thereby mitigating tumor hypoxia and downregulating hypoxia-inducing factors (HIF-1α). Due to the presence of porphyrin ligands in PCN-224, the generated O 2 can be further converted to toxic singlet oxygen ( 1 O 2 ) under laser irradiation. Additionally, the platform allows near-infrared (NIR) fluorescence imaging, providing real-time information on intracellular GSH changes during PDT and ferroptosis. The PAMH nanoplatform has shown effective inhibition of tumor growth in subcutaneous models via both intravenous and intratumoral injection, indicating its potential in modulating reactive oxygen/sulfur species and reshaping TME, thereby facilitating imaging-guided cascaded nanocatalytic therapy.
研究领域:
纳米医学
·
癌症治疗
·
生物化学
·
材料科学
·
成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Tingjie Yin,Jiyong Liu,Zekai Zhao,Lihui Dong,Han Cai,Lifang Yin,Jianping Zhou,Meirong Huo
Co-delivery systems capable of transporting hydrophobic chemotherapeutics and hydrophilic siRNA to the same cell population with simultaneous burst release of both drugs to maximize synergistic anticancer efficacy remains elusive. In this light, a multifunctional nanoparticle (HA-PSR) consisting of a redox-sensitive core and detachable crosslinked hyaluronic acid (HA) shell was developed. Octyl modified PEI containing disulfide linkages (PSR) were synthesized as the core materials for co-encapsulation of chemotherapeutics and siRNA, while a HAase-sensitive thiolated HA (HA-SH) was collaboratively assembled to the anionic shell for CD44-mediated active targeting along with enhanced and detachable protection for drug loaded inner cores. Resultantly, HA de-protected redox-sensitive inner cores achieved co-burst release of both cargoes when triggered by glutathione (GSH) rich environments in cytoplasm. Results of in-vivo and in-vitro testing indicated successful co-encapsulation of hydrophobic drugs and hydrophilic siRNA with adjustable ratios. Selective delivery to CD44 overexpressing tumors was achieved through passive and active targeting, followed by HAase-triggered HA de-shielding and GSH-triggered burst release of both cargos. Rapid intracellular trafficking maximized synergistic cytotoxicities of chemotherapeutics and siRNA for remarkable tumor inhibition in a xenograft animal tumor model. Consequently, the HA-PSR nanoparticle holds great potential for combined chemotherapeutics/siRNA treatment in cancer with maximized synergistic antitumor efficacy.
研究领域:
纳米技术
·
癌症研究
·
药学科学
·
分子生物学
✓ 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）