BIOMATERIALS
·
2025
·
IF 12.9
Jingchuan He,Tingting Li,Xiaoqin Pan,Zhihua Deng,Jifu Huang,Xiaocheng Mo,Xiaoju Shen,Xiumei Qin,Xingye Yang,Ming Gao,Jie Yang
Combination therapy is a promising strategy for lung adenocarcinoma (LUAD), due to the advantages of overcoming drug resistance, side effects, and tumor heterogeneity. Herein, we report a novel dual-targeting bimetallic nanozyme (MH-iRGD) consisting of nanosized manganese ferrite (MF) after encapsulating with dopamine and methacrylic anhydride to modify hyaluronic acid, followed by integrin receptor targeting peptide (HS-PEG3400-iRGD) modification for LUAD targeted therapy. Our study confirmed that MH-iRGD combined with near-infrared irradiation (NIR) possessed dramatic photothermal effects and reactive oxygen species (ROS) production and GSH depletion abilities. Importantly, MH-iRGD possessed dual-targeting capacities for LUAD cells overexpressed CD44 and αV-integrin receptors owing to hyaluronic acid coating and iRGD modification. Inhibitors of CD44 and integrins could impair the uptake of MH-iRGD in LUAD cells. Moreover, MH-iRGD+NIR displayed excellent anti-LUAD effects as a result of the production of intracellular ROS, consumption of glutathione (GSH) and mitochondrial dysfunction. Mechanistically, NIR robustly strengthened MH-iRGD-induced ferroptosis and apoptosis by down-regulating SLC7A11, GPX4, Bcl-2 levels while up-regulating Bax level. Specifically, ferroptosis and apoptosis were increased while the LUAD progression was inhibited after intravenous injection of MH-iRGD+NIR in xenograft mouse models. Taken together, our results indicate that MH-iRGD+NIR serves as a promising targeted therapy for LUAD, which broadens the applications of highly active dual-targeting bimetallic nanozymes.
研究领域:
肿瘤学
·
生物材料学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Xue Dong,Shaohua Zou,Chunjing Guo,Kaili Wang,Feng Zhao,Huaying Fan,Jungang Yin,Daquan Chen
The traditional therapy of cancer has systemic side effects, and many cancers, such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumours. This study was aimed at enhancing the anti-tumour effect of curcumin (CUR) and preventing tumour spread to the bone. A novel multifunctional redox-responsive and CD44 receptor targeting polymer-drug, poly alendronate-hyaluronan-S-S-curcumin copolymer (ALN-oHA-S-S-CUR) based CUR and alendronate (ALN) were synthesized successfully with the disulphide bond linker. The structure of ALN-oHA-S-S-CUR was characterized by 1H-NMR. The nanomedicine had natural anti-tumour drugs (CUR) as the hydrophobic kernel, and targeting CD44 receptor oligosaccharides of hyaluronan (oHA) and other anti-tumour drugs (ALN) as hydrophilic shell, named ALN-oHA-S-S-CUR conjugates, which could self-assemble into micelle-like nano-spheres in water via a dialysis method with hydrodynamic diameters of 179 ± 23 nm. Interestingly, the cur-loaded ALN-oHA-S-S-CUR micelles were stable in PBS but were capable of releasing the drug under the reducing environment. The rate of drug release was proportional to the GSH concentration. The uptake and cytotoxicity of micelles were higher in MDA-MB-231 cells than in MCF-7 cells because of a higher expression of the CD44 receptor in the former cell line. And compared to the cur-loaded oHA-CUR micelles, the cur-loaded ALN-oHA-S-S-CUR micelles had a good cellular uptake in 2D cancer cell and penetrability in 3D cancer cell spheroids. These results indicated the active targeting redox-sensitive micelles were promising as intracellular drug delivery systems for cancer treatment.
研究领域:
药学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Meijia Song,Yan Liang,Keke Li,Jing Zhang,Nan Zhang,Baocheng Tian,Jingtian Han
Tumor targeted drug delivery system has been developed as a promising approach to improve cancer chemotherapy . The design of hyaluronic acid (HA)-modified nanocarriers has been proven to be effective for targeting CD44 overexpressing tumor cells. Moreover, combination therapy can improve the therapeutic effect and delay the development of drug resistance. In this study, doxorubicin (DOX) and paclitaxel (PTX) co-loaded liposomal delivery system modified with an acid-cleavable cholesterol-HA conjugate (Chol-HA) was prepared by post-insertion method. The dual-drug co-loaded HA modified liposome (HA-D/P-Lip), had a suitable particle size of 125.5 ± 0.79 nm with negative surface charge of −9.56 ± 0.62 mV, and acceptable encapsulation efficacy of 93.6 ± 0.51% (DOX) and 70.4 ± 1.46% (PTX). In vitro drug release study showed that the cumulative release of both drugs over 72 h were much higher in pH 5.5 phosphate buffer than that in pH 7.4 phosphate buffer. In vitro cytotoxicity study against MCF-7 breast cancer cells illustrated superior cytotoxicity and obvious synergistic effect in comparison to free drug or single drug loaded liposome via MTT assay. In vitro cellular uptake study demonstrated a higher cell internalization of HA-DOX-Lip compared with DOX loaded non-modified liposome (DOX-Lip) and free DOX. Therefore, the pH-sensitive HA-targeted liposome may be a useful targeted nanocarrier for efficient tumor therapy.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Chen-Lin Feng,Yan-Xing Han,Hui-Hui Guo,Xiao-Lei Ma,Zhi-Qiang Wang,Lu-Lu Wang,Wen-Sheng Zheng,Jian-Dong Jiang
Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self-assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex. In vitro physiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle at G0/G1 phase and suppression of cancer cell proliferation as well as colony formation. Furthermore, in vivo distribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, following in situ application. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC.
研究领域:
生物医学工程
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肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Clinical and Translational Medicine
·
2022
·Vol. 12
·期 4
·e836
·
IF 8.554
Yuechao Liu,Yang Song,Mengru Cao,Weina Fan,Yaowen Cui,Yimeng Cui,Yuning Zhan,Ruixue Gu,Fanglin Tian,Shuai Zhang,Li Cai,Ying Xing
Background There is growing evidence that endocytosis plays a pivotal role in cancer metastasis. In this study, we first identified endocytic and metastasis-associated genes (EMGs) and then investigated the biological functions and mechanisms of EMGs. Methods Cancer stem cells (CSCs)-like characteristics were evaluated by tumour limiting dilution assays, three-dimensional (3D) spheroid cancer models. Microarray analysis was used to identify the pathways significantly regulated by mammalian Eps15 homology domain protein 1 (EHD1) knockdown. Mass spectrometry (MS) was performed to identify EHD1-interacting proteins. The function of EHD1 as a regulator of cluster of differentiation 44 (CD44) endocytic recycling and lysosomal degradation was determined by CD44 biotinylation and recycling assays. Results EHD1 was identified as a significant EMG. Knockdown of EHD1 suppressed CSCs-like characteristics, epithelial–mesenchymal transition (EMT), migration and invasion of lung adenocarcinoma (LUAD) cells by increasing Hippo kinase cascade activation. Conversely, EHD1 overexpression inhibited the Hippo pathway to promote cancer stemness and metastasis. Notably, utilising MS analysis, the CD44 protein was identified as a potential binding partner of EHD1. Furthermore, EHD1 enhanced CD44 recycling and stability. Indeed, silencing of CD44 or disruption of the EHD1/CD44 interaction enhanced Hippo pathway activity and reduced CSCs-like traits, EMT and metastasis. Interestingly, specificity protein 1 (SP1), a known downstream target gene of the Hippo-TEA-domain family members 1 (TEAD1) pathway, was found to directly bind to the EHD1 promoter region and induce its expression. Among clinical specimens, the EHD1 expression level in LUAD tissues of metastatic patients was higher than that of non-metastatic patients. Conclusions Our findings emphasise that EHD1 might be a potent anti-metastatic target and present a novel regulatory mechanism by which the EHD1/CD44/Hippo/SP1 positive feedback circuit plays pivotal roles in coupling modules of CSCs-like properties and EMT in LUAD. Targeting this loop may serve as a remedy for patients with advanced metastatic LUAD.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xianshuo Zhang,Peipei Wang,Xinsheng Wang,Yaoyu Xu,Taolin Cheng,Chengjie Zhang,Jiaying Ding,Yunfeng Shi,Wei Ma,Cui-Yun Yu,Hua Wei
Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility , biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β -cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly( ε -caprolactone)- b -poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL- b -PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL- b -PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% ( P1 ) and 20 wt% ( P2 ) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1 -based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1 -based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.
研究领域:
纳米医学
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癌症研究
·
药物递送系统
·
材料科学
✓ 已验证
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2015
·
IF 2.711
Xin Wang,Ying Liu,Shouju Wang,Donghong Shi,Xianguang Zhou,Chunyan Wang,Jiang Wu,Zhiyong Zeng,Yanjun Li,Jing Sun,Jiandong Wang,Longjiang Zhang,Zhaogang Teng,Guangming Lu
Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2016
·
IF 4.843
Daquan Chen,Shengnan Lian,Jingfang Sun,Zongliang Liu,Feng Zhao,Yongtao Jiang,Mingming Gao,Kaoxiang Sun,Wanhui Liu,Fenghua Fu
In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Zhan Su,Duanqin Liu,Liying Chen,Jun Zhang,Lu Ru,Zhiyu Chen,Zhennan Gao,Xuxia Wang
Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment.Methods We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice.Results The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid.Conclusion These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yuqi Wu,Jiawei Li,Liang Liu,Xinhong Chu,Min Zhong,Hongkun Li,Chengcheng Zhao,Hui Fu,Yujiao Sun,Yingpeng Li
The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Bulletin
·
2017
·
IF 4.092
Xiaojuan Yang,Rongcheng Zhou,Yan Hao,Peihui Yang
A sensitive CD44-biosensor based on quartz crystal microbalance (QCM) was proposed for evaluating metastatic potential of breast cancer cells by using hyaluronan (HA) functionalized substrate film, polydopamine and polyethyleneimine composite film, for the purpose of capturing CD44-positive cancer cells through specific binding of HA to CD44 . Two differently CD44-expressed breast cancer cell lines (MDA-MB-231 cells and MCF-7 cells) were put to use as targets for quantitative analysis as well as evaluation of metastatic potential of the cells. The limit of detection for MDA-MB-231 (M231) cells and MCF-7 cells were 300 and 1,000 cells mL −1 , respectively. The expression level of CD44 on M231 cells exhibited two times higher than that of MCF-7 cells, indicating of a higher metastatic potential. Moreover, poly- L -lysine modified QCM sensor was applied to monitor the stiffness of breast cancer cells that can reflect metastatic potential of cells. The results revealed that the MCF-7 cells were stiffer than M231 cells, implying that the M231 cells possessed higher metastatic potential. The proposed protocol is simple and rapid to evaluate the metastatic potential of cancer cells, in addition to offering a promising diagnostic tool for metastatic cancer.
研究领域:
肿瘤学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 70
·40873-40882
·
IF 3.049
Lu Diao,Ao Shen,Yunxu Yang,Jin Tao,Ying Hu
Chemotherapeutic drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the two most common mechanisms leading to chemotherapy resistance. In this study, we focused on the applicability of curcumin (CUR) as a sensitizer for chemotherapeutics (doxorubicin [DOX] as the model drug) modified with hyaluronic acid (HA) as an effective therapeutic strategy against multidrug resistance (MDR) in cancer cells. We constructed an HA–CUR/DOX delivery system measuring approximately 180 nm with superior encapsulation efficacy and serum stabilities. In vitro, we found that HA modification could facilitate the efficient delivery of chemotherapeutics through CD44 receptor-mediated targeted delivery. MTT assay results confirmed that the combination of CUR and DOX/paclitaxel (PTX) had a significant synergistic effect and significantly reversed MDR. Further experiments including real-time polymerase chain reaction and western blotting proved that the main mechanisms by which CUR reversed MDR in tumor cells were inhibiting the expression and activity of P-glycoprotein (P-gp) and inducing apoptosis through mitochondrial pathway. Taken together, our new engineered tumor-targeting nanoparticle delivery system may have the potential for overcoming MDR in cancer.
研究领域:
肿瘤学
·
药学
·
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）