BIOMATERIALS
·
2018
·
IF 8.806
Chunqi Zhu,Hanbo Zhang,Wei Li,Lihua Luo,Xiaomeng Guo,Zuhua Wang,Fenfen Kong,Qingpo Li,Jie Yang,Yongzhong Du,Jian You
The treatment of metastatic cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in tumor have always been our pursuit in cancer therapy, especially to advance cancer with metastasis, for increasing the efficacy and biosafety. We established a smart nanosized micelle , formed by tocopherol succinate (TOS) conjugated hyaluronic acid (HA) using a disulfide bond linker. The micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed tumor, and response selectively to high GSH level in the cells, inducing disulfide bond breakage and the release of the payload (paclitaxel, PTX). To predict the antitumor efficacy of the micelles more clinically, we established an orthotopic colon cancer model with high metastasis rate, which could be visualized by the luciferase bioluminescence . Our data confirmed CD44 high expression in the colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of cancer cells in intestines demonstrated an exact recognition of our micelles to orthotopic colon tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released Nile Red from the micelles was found only in the tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the cancer cells, indicating a highly selective drug release. Our micelles presented an excellent therapeutic effect against metastatic colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced cancers with high CD44 receptor expression.
研究领域:
癌症治疗
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Yijue Wang,Liqing Zou,Zhe Qiang,Jianhai Jiang,Zhengfei Zhu,Jie Ren
Radiotherapy (RT) is a major treatment method for non-small-cell lung cancer (NSCLC), and development of new treatment modality is now critical to amplify the negative effects of RT on tumors. In this study, we demonstrated a nanoparticle-loaded block copolymer micellar system for cancer hyperthermia treatment (HT) that can be used for synergistic therapy under alternating magnetic field (AMF) and radiation field. Block copolymer micelles (polyethylene glycol-block-polycaprolactone, or PEG-PCL) containing hyaluronic acid (HA) and Mn–Zn ferrite magnetic nanoparticles (MZF) were fabricated via a two-step preparation. HA-modified Mn–Zn ferrite magnetic nanoparticles (MZF-HA) can be enriched in CD44 highly expressing tumor cells, such as A549 (human lung adenocarcinoma cell line), through an active targeting mechanism via receptor–ligand binding of HA and CD44 (HA receptor). MZF can generate thermal energy under an AMF, leading to a local temperature increase to approximately 43 °C at tumor sites for mild HT, and the increased tumor oxygenation can enhance the therapeutic effect of RT. In vitro experiments show that MZF-HA is able to achieve excellent specific targeting performance toward A549 cells with excellent biocompatibility as well as enhanced therapy performance under HT and RT in vitro by apoptosis flow cytometry. In the A549 subcutaneous tumor xenografts model, MRI confirms the enrichment of MZF-HA in tumor, and hypoxia immunohistochemistry analysis (IHC) proved the increased tumor oxygenation after HT. Furthermore, the tumor volume decreases to 49.6% through the combination of HT and RT in comparison with the 58.8% increase of the untreated group. These results suggest that the application of MZF-HA is able to increase the therapeutic effect of RT on A549 and can be used for further clinical NSCLC treatment evaluation.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
·
癌症治疗
·
材料科学
✓ 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
BIOMATERIALS
·
2020
·
IF 10.317
Kang Qin,Fei Wang,Russell M.L. Simpson,Xueni Zheng,He Wang,Yanhua Hu,Zhixian Gao,Qingbo Xu,Qiang Zhao
The regeneration of smooth muscle with physiological functions has been a key challenge in vascular tissue engineering . Hyaluronan (HA), as a major component of the extracellular matrix, plays a vital role in regulating tissue injury and repair. In this study, a biomimetic vascular graft was prepared by co-electrospinning of synthetic degradable polymers and native ECM components including collagen type-I as well as low and high molecular weight HA (LMW HA and HMW HA). Upon implantation in the rat abdominal aorta, the grafts exhibited sustained HA release that effectively enhanced the regeneration of vascular smooth muscle. Besides, LMW HA loaded vascular grafts demonstrated rapid endothelialization compared to the other groups. More importantly, HA-loaded poly(L-lactide-co-caprolactone) grafts demonstrated an optimal vascular media layer accompanied by well-organized elastin fibers after long-term implantation (6 months), and they maintained potent physiological function up to 1/3 that of the native artery . In contrast, inadequate smooth muscle regeneration was observed in poly(ε-caprolactone) grafts due to slow degradation restricting the regeneration. The mechanism was further investigated and explained by the HA-induced migration of smooth muscle cell (SMC) via CD44-mediated signaling. Besides, low molecular weight HA can promote the migration of vascular progenitor cells that further differentiate into SMCs. These results highlight the importance of HA in the regeneration of functional vascular smooth muscle, and provide a new insight into the fabrication of tissue engineering vascular grafts (TEVGs) via combining rapidly degradable polymers and bioactive ECM components that hold great translational potential.
研究领域:
组织工程
·
生物材料
·
血管生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xue Yang,Fang Gao,Wenan Zhang,Huipeng Li,Xinzhi Huang,Jiajia Wei,Jiayi Bian,Ying Yang,Chenggen Qian,Minjie Sun
Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer , CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.
研究领域:
肿瘤学
·
分子生物学
·
药学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2021
·
IF 6.598
Shanshan Xu,Chunyu Liu,Shuya Zang,Jiaxin Li,Yashi Wang,Kebai Ren,Man Li,Zhirong Zhang,Qin He
Metastasis is closely related to the high mortality of cancer patients, which is regulated by multiple signaling pathways. Hence, multiphase blocking of this biological process is beneficial for cancer treatments. Herein, we establish a multifunctional self-delivering system by synthesizing D -α-tocopheryl succinates (TOS)-conjugated chondroitin sulfate (CS) (CT NPs), which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade. TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9, while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets. The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade. Following encapsulating chemotherapeutic drug doxorubicin (DOX), the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice. As a result, the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases.
研究领域:
药学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 9
·1174
·
IF 4.9
Siying Huang,Simeng Xiao,Xuehao Li,Ranran Tao,Zhangwei Yang,Ziwei Gao,Junjie Hu,Yan Meng,Guohua Zheng,Xinyan Chen
Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
·
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
·
2017
·
IF 4.164
Huimin Zhou,Haixing Xu,Xin Li,Yahui Lv,Tian Ma,Shiying Guo,Zhijun Huang,Xiaobing Wang,Peihu Xu
This work reports a multifunctional nanoplatform ( [email protected] 2 -HA-RGD) by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica-coated gold nanorods ( [email protected] 2 ) for dual-targeted chemo-photothermal therapy. Doxorubicin hydrochloride (DOX) was used as the model drug to investigate the drug loading, in vitro drug release profiles and cell evaluation. The nanoplatform has demonstrated a good photothermal effect and excellent drug loading capacity of about 20.16%. It also had pH-enzyme sensitive and NIR-triggered drug release properties. Cellular uptake experiment results indicated that [email protected] 2 -HA-RGD can be dual-targeted to ovarian cancer cells via CD44 and integrin receptor mediated endocytosis pathway. Cytotoxicity experiments demonstrated that combined therapy exhibited a better therapy effect compared to that of single chemotherapy or photothermal therapy. Our study demonstrates that [email protected] 2 -HA-RGD may be a new promising dual-targeted delivery system for chemo-photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
✓ 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
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2018
·Vol. 33
·期 2
·512-523
·
IF 0.524
Zhou Huimin,Gao Yuxiang,Xu Haixing,Li Xin,Lü Yahui,Ma Tian,Cai Xinjie,Li Rui,Wang Xiaobing,Xu Peihu
A multifunctional drug delivery system (GNRs@mSiO 2 -HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO 2 ) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1 H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO 2 -HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has pH-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO 2 -HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@ mSiO 2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO 2 -HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO 2 -HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Chengcheng Wang,Jiao Wang,Xue Pan,Shuang Yu,Meiqi Chen,Yan Gao,Zilin Song,Haiyang Hu,Xiuli Zhao,Dawei Chen,Fei Han,Mingxi Qiao
As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense. MOF nanoparticle was constructed by the photosensitizer of [4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid)] (TCPP) and the metal ion of Zr6, which was further decorated with hyaluronic acid (HA) in order to impart active targeting to CD44 receptors overexpressed cancer cells. BMH exhibited a negative charge and spherical shape with average particle size about 162.5 nm. BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation. This was attributed to the combination of photodynamic therapy (PDT) and γ-glutamylcysteine synthetase inhibitor of BSO, shifting the redox balance to oxidative stress. Enhanced ferroptosis also induced the release of damage associated molecular patterns (DAMPs) to maturate dendritic cells and activated T lymphocytes, leading to superior anti-tumor performance in vivo . Taken together, our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.
研究领域:
癌症生物学
·
纳米医学
·
药学
·
细胞生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Chang Ni,Zijun Zhang,Yuling Wang,Zhenhai Zhang,Xueping Guo,Huixia Lv
Hyaluronic acid (HA) has been widely used in cosmetics and topical preparations owing to its favorable moisturizing property and potential in enhancing drugs' skin permeability. Here, the influencing factors and underlying mechanism of HA on skin penetration were carefully investigated, and HA-modified Undecylenoyl-Phenylalanine (UP) liposomes (HA-UP-LPs) were designed as a proof of principle for efficacious transdermal drug delivery strategy to enhance the skin penetration and retention. An in vitro penetration test (IVPT) of HA with different molecular weights showed that low molecular weight HA (LMW-HA, 5 kDa and 8 kDa) could pass through the stratum corneum (SC) barrier and enter into the epidermis and dermis layers, whereas its high molecular counterparts (HMW-HA) were trapped on the SC surface. Mechanistic studies revealed that LMW-HA could interact with keratin and lipid in the SC meanwhile exerted a substantial skin hydration effect, which may partially contribute to the SC penetration benefit. In addition, the surface decoration of HA drove an energy-dependent caveolae/lipid raft-mediated endocytosis of the liposomes through direct binding to the CD44 receptors widely expressed on skin cell membranes . Notably, IVPT showed a 1.36-fold and 4.86-fold increase in skin retention of UP and a 1.62-fold and 5.41-fold increase in skin penetration of UP with HA-UP-LPs over UP-LPs and free UP at 24 h, respectively. As a result, the anionic HA-UP-LPs (−30.0 mV) showed enhanced drug skin penetration and retention compared with conventional cationic bared UP-LPs (+21.3 mV) on both in vitro mini-pig skin as well as in vivo mouse skin. Overall, the usage of LMW-HA might offer opportunities in developing novel topical preparations and skin care products with improved transdermal penetration and retention.
研究领域:
药剂学
·
化妆品科学
·
药物递送系统
·
生物药剂学
✓ 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）