Nano Research
·
2017
·Vol. 11
·期 2
·929-939
·
IF 7.354
He Zhimei,Zhang Penghui,Xiao Yan,Li Jingjing,Yang Fang,Liu Yang,Zhang Jian-Rong,Zhu Jun-Jie
During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T 1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and “turned on” T 1 signals in vitro , showing great promise for diagnosis and treatment.
研究领域:
癌症治疗
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纳米技术
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药物递送系统
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磁共振成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yanhai Xi,Tingwang Jiang,Yinglan Yu,Jiangmin Yu,Mintao Xue,Ning Xu,Jiankun Wen,Weiheng Wang,Hailong He,Yan Shen,Daquan Chen,Xiaojian Ye,Thomas J Webster
Introduction Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity.Methods The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied.Results The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR.Conclusion The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.
研究领域:
药学
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生物医学工程
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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
Burns & Trauma
·
2021
·
IF 5.099
Liu Lu,Shao Yiming,Zhang Yixuan,Yang Yunxi,Huang Jiamin,Li Linbin,Sun Ran,Zhou Yuying,Su Yicheng,Sun Bingwei
BackgroundBurn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury. However, the pathophysiological mechanism of vascular leakage is still unclear. The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.MethodsNeutrophils were isolated from human peripheral blood by magnetic beads sorting. ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma. The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice, and high-quality video were provided. Adhesion-related molecules were investigated by qRT-PCR. The damage to glycocalyx of mice vascular endothelial cells was observed by transmission electron microscope and scanning electron microscope. Proteomic analysis, flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite (HOCl) and CD44 of human vascular endothelial cells.ResultsIn this study, we found that rapidly increasing activated neutrophils secrete heparin binding protein (HBP) and myeloperoxidase (MPO) after severe burn injury. Increased HBP triggers vascular leakage with synergy of MPO, results in systemic edema and burn shock. Furthermore, we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx. Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage. However, MPO inhibitors partially protect the glycocalyx of vascular endothelial cells. The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.ConclusionsTaken together, these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns. Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.
研究领域:
免疫学
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病理生理学
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烧伤与创伤
·
血管生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Shasha Yang,Zhihuan Zhao,Yiliang Xie,Jianying Lin,Bing Zhang,Jimin Fan
In this study, a biodegradable multifunctional photothermal drug delivery nanoparticles (MPH NPs) using curcumin (Cur) as the ligand coated with hyaluronic acid (HA) was successfully prepared, which could simultaneously deliver Cur and doxorubicin hydrochloride (DOX·HCl) to overcome the common drug resistance in cancer cells. Polydopamine (PDA) as a protective shell prevents premature degradation of Cur in physiological environment and enables it to play effective medicinal value. MPH NPs can specifically recognize CD44 receptors on the surface of cancer cells for tumor targeting, with the damage of the partially released DOX to the superficial tumor cells, and then the positively charged Cur released may gradually penetrate into the cells through electron interaction to improve the problem of low permeability. In vitro cell experiments showed that hydrophobic/hydrophilic drugs co-loaded MPDH (MPH loaded with DOX·HCl) could enter the cancer cells through the endocytosis mediated by clathrin / caveolin, and the inhibition rate of MPDH on HeLa cells reached 79.28 % irradiation under 808 nm laser. MPH were composed of safe materials that have been proven to be biodegradable in human body, which avoided the disadvantages that NPs were difficult to discharge and caused damage to normal organs during long-term use.
研究领域:
生物医学工程
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纳米医学
·
药学
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肿瘤学
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药物递送系统
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材料科学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianhua Wang,Qiang Hou,Jie Qu,Xueping Huo,Huiting Li,Yangmeng Feng,Qiyu Wang,Le Chang,Cuixiang Xu
Gastric cancer is a prevalent malignant tumor worldwide, posing challenges due to its poor prognosis and limited treatment options. Cancer stem cells (CSCs) were demonstrated as a subset of cancer cells responsible for tumor initiation and progression, and their inherent resistance to conventional chemotherapy and radiotherapy critically contributes to tumor recurrence and metastasis. Promoting the eradication of cancer stem cells is crucial for enhancing the efficacy of cancer treatments. This study introduces a novel therapeutic strategy utilizing polyhedral magnetic nanoparticles (PMNPs) functionalized with CD44 antibodies and cell-penetrating peptides (CPPs) to improve uptake by gastric cancer stem cells (MCSCs). PMNPs, synthesized via thermal decomposition, exhibited a diameter of 90 nm ± 9 nm and a saturation magnetization of 79.9 emu/g. Functionalization enhanced their uptake capabilities. Under a rotating magnetic field (RMF) of 15 Hz, PMNPs disrupted cellular structure, leading to apoptosis and ferroptosis in MCSCs. The in vitro studies showed significant reduction in MCSCs viability , while in vivo studies demonstrated tumor growth suppression with minimal side effects and high biocompatibility . This work presents a novel strategy for designing magnetic nanoparticles to mechanically destroy cancer stem cells, offering a more efficient and safety treatment option for gastric cancer.
研究领域:
肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
✓ 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
Xia Chen,David H. Bremner,Yuhan Ye,Jiadong Lou,Shiwei Niu,Li-Min Zhu
The premature leakage of chemotherapeutics during delivery impedes drugs from entering tumor cells, which produces considerable side effects in normal organs. Herein, we describe a hydrophobic-hydrophilic balanced self-assembled prodrug nanoparticle ( [email protected] ), formed via a facile synthesis based on chitosan oligosaccharide to reduce the non-targeting risk of premature leakage of chemotherapeutics during their delivery. The [email protected] have a suitable size (~186 nm) with a doxorubicin (DOX) loading of 9.88% and an oleanolic acid (OA) loading efficiency of 27.34%. The release of DOX or OA is pH-dependent and responds particularly well to the acidic tumor microenvironment. In vitro antitumor activity studies revealed that [email protected] had enhanced performance in promoting tumor apoptosis and displayed significant anticancer effects compared to mono-delivery. In vitro cell studies showed that HA-functionalized nanoparticles could enhance the cellular uptake in tumor cells. Therefore, [email protected] is a promising vehicle for CD44-targeted co-delivery of cancer chemotherapy, which deserves further evaluation.
研究领域:
药剂学
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纳米技术
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肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Xianqi Zhu,Lin Li,Jin Tang,Chunyu Yang,Hao Yu,Kunpeng Liu,Ziyan Zheng,Xinggui Gu,Qingsong Yu,Fu-Jian Xu,Zhihua Gan
Metastasis has been widely recognized as the most lethal threats for cancer patients . Due to their special genetic and environmental context, cancer stem cells (CSCs) which are resistant to most cytotoxic drugs and radiation, are considered as the dominant culprit for metastasis. Thus, the efficient targeting and thorough elimination of CSCs are significantly urgent for the enhancement of therapeutic efficacy. Herein, we developed a facile and smart photothermal-chemo therapeutic nano-assembly system, of which the surface was modified by a sheddable PEG shell and acid-activatable pro-penetration peptide, to surmount the physiological barriers in targeting CSCs. A highly-efficient diradical-featured croconium-based photothermal agent and a natural cytotoxic heat shock protein (HSP) inhibitor were co-loaded in redox-sensitive chitosan matrices to realize the synergistic photothermal-chemo therapy. Within solid tumors, the PEG shell that prevents the nano-assembly from mononuclear phagocytic clearance could rapidly leave to expose the positively charged chitosan, and the detached iRGD could further actuate the tumor penetration of chitosan nanoparticles , and allow the CSCs targeting by selective recognition of CD44 protein. Owing to the HSP inhibition and chemo-sensitization, both the CSCs and non-CSCs could be thoroughly eliminated by the designed nano-assembly, largely inhibiting the tumor growth and metastasis. This work provides a potential strategy for CSCs-targeting drug delivery to solve the CSCs-related metastasis.
研究领域:
肿瘤学
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纳米技术
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药物递送系统
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 104
·101790-101799
·
IF 3.289
Lijun Kong,Zezhong Mu,Yuan Yu,Lixia Zhang,Jinxia Hu
Targeted delivery of therapeutic drugs into cancer cells is a facile method to improve therapeutic efficacy. Focused on this point, a functionalized porous hydroxyapatite (HAp) nanoparticle-based nanocarrier consisting of polyethyleneimine (PEI) coating and outer hyaluronic acid (HA) modification (HAp–PEI–HA) has been developed. In this nanocarrier, PEI was coated onto the HAp to stabilize the nanoparticles, and HA acted as an efficient targeting ligand to selectively bind the CD44 receptors which are overexpressed on the surface of some cancer cells. Various techniques demonstrated the successful preparation of the HAp–PEI–HA nanoparticles. The resulting HAp–PEI–HA nanoparticles showed better dispersibility and stability in aqueous solution compared to bare HAp. In addition, the DOX released from DOX@HAp–PEI–HA exhibited a pH-responsive release profile. The targeting property of HAp–PEI–HA was investigated on A549 cells with high CD44 receptor expression and U87 cells with low CD44 receptor expression. The result showed enhanced cellular uptake of HAp–PEI–HA nanoparticles in A549 cells through CD44 receptor mediated cellular endocytosis. Furthermore, the effective targeted delivery of DOX by HAp–PEI–HA in A549 cells led to enhanced therapeutic efficacy. Thus, the designed HAp–PEI–HA nanocarrier showed promising potential for targeted drug delivery in cancer therapy.
研究领域:
纳米技术
·
药剂学
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癌症研究
·
生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Yanbo Yang,Jianrong Wu,David H. Bremner,Shiwei Niu,Yu Li,Xuejing Zhang,Xiaotian Xie,Li-Min Zhu
Synergistic tumor treatment has recently attracted more and more attention due to its remarkable therapeutic effect. Herein, a multifunctional drug delivery system based on hyaluronic acid (HA) targeted dual stimulation responsive MoS 2 nanosheets (HA-PEI-LA-MoS 2 -PEG, HPMP) for active interaction with CD44 receptor positive MCF-7 cells is reported. Melanin (Mel), a new type of photothermal agent and doxorubicin (DOX) are both loaded onto the HPMP nanocomposite and can be released by mild acid or hyperthermia. The prepared HPMP nanocomposite has a uniform hydrodynamic diameter (104 nm), a high drug loading (944.3 mg.g −1 HPMP), a remarkable photothermal effect (photothermal conversion efficiency: 55.3%) and excellent biocompatibility. The DOX release from HPMP@(DOX/Mel) can be precisely controlled by the dual stimuli of utilizing the acidic environment in the tumor cells and external laser irradiation. Meanwhile, loading of Mel onto the surface can enhance the photothermal effect of the MoS 2 nanosheets. In vitro experiments showed that the HPMP@(DOX/Mel) nanoplatform could efficiently deliver DOX into MCF-7 cells and demonstrated enhanced cytotoxicity compared to that of the non-targeted nanoplatform. In vivo experiments in a breast cancer model of nude mice further confirmed that the HPMP@(DOX/Mel) significantly inhibited tumor growth under near infrared (NIR) laser irradiation, which is superior to any single therapy. In summary, this flexible nanoplatform, based on multi-faceted loaded MoS 2 nanosheets, exhibits considerable potential for efficient pH/NIR-responsive targeted drug delivery and chemo-photothermal synergistic tumor therapy.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
光热疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Zhaoyu Han,Yue Qian,Xiyue Gao,Dutao Yang,Yanfei Cai,Yun Chen,Jian Jin,Zhaoqi Yang
In recent years, laser-mediated photodynamic therapy and photothermal therapy have attracted widespread attention due to their minimally invasive, easy to operate characteristics and high specificity. However, the traditional photodynamic or photothermal therapy exist several shortcomings such as the hypoxic microenvironment, intracellular heat shock proteins or complex operation. In this study, covalent organic framework (COF) was used as the drug carrier to equip with the photosensitizer indocyanine green (ICG) and the hypoxia-activating prodrug AQ4N. The hyaluronic acid (HA) was modified on the surface of COF to obtain the [email protected] /AQ4N drug delivery system. HA-modified COF delivery systems can target tumor cells through recognize CD44 which is overexpressed in the surface of tumor cells membrane . Under the irradiation of single NIR laser , ICG that can excite the nanoplatform simultaneously produces a combined effect of photodynamic and photothermal. At the same time, photodynamic therapy through depleting intracellular oxygen exacerbates the hypoxic state of the tumor microenvironment, which in turn enhances AQ4N reduced to chemotherapeutic drug AQ4, producing a synergistic cascade antitumor effect . The results of our study by tumor cell and tumor spheroids indicated that the hypoxia-activated multi-functional nanoplatform could effectively inhibit the growth and metastasis of triple-negative breast cancer.
研究领域:
癌症治疗
·
材料科学
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生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Mang Mang Sang,Fu Lei Liu,Yang Wang,Ren Jie Luo,Xiao Xian Huan,Ling Fei Han,Zhong Tao Zhang,Feng Feng,Wei Qu,Wenyuan Liu,Feng Zheng
Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor biocompatibility. In the present study, a novel of redox/pH dual-responsive multifunctional magnetic complex micelle (sPEG/HA/CSO-SS-Hex/Fe3O4/GA), which consisted of a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and DCA grafted sheddable PEG-PLL (sPEG) copolymers and loaded with gambogic acid (GA) and Fe3O4 nanoparticles were developed for parenteral delivery for the treatment of triple negative breast cancer (TNBC). The ex vivo study showed that the sPEG shielded cationic HA/CSO-SS-Hex/Fe3O4/GA core at physiological pH but quickly shed off to re-expose the core due to its charge reversible property. The sPEG/HA/CSO-SS-Hex/Fe3O4/GA micelles effectively facilitated tumor-targeted GA delivery by HA, which is a targeting ligand for CD44 receptor of TNBC cells, meanwhile increase GA uptake at the acidic condition but diminished the drug uptake at neutral pH. The in vitro cellular uptake study and in vivo biodistribution and antitumor activity of the formulations were determined, all results showed that the complex micelle enhanced TNBC tumor cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated internalization and redox/pH dual-responsive drug release. Hence, tumor-targeted delivery of GA with redox/pH dual-responsive multifunctional magnetic complex micelle sPEG/HA/CSO-SS-Hex/Fe3O4/GA might have potential implications for the chemotherapy of TNBC.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·562-570
·
IF 6.331
Shun Liu,Yun Zhao,Meili Shen,Yujiao Hao,Xiaodong Wu,Yixuan Yao,Yapeng Li,Qingbiao Yang
Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical–photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil–water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical–photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.
研究领域:
纳米技术
·
药学
·
心血管疾病
✓ 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）