JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jinghua Sun,Xuhui Zhao,Hao Shen,Jie Dong,Shuo Rong,Wenwen Cai,Ruiping Zhang
Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a serious kidney disease with high morbidity and mortality. However, there is no effective clinical treatment strategy. Herein, we developed a CD44 targeting nanoplatform based on HA-assembled melanin NPs covalently coupled with dexamethasone for I/R-induced AKI therapy by alleviating oxidative/inflammatory- induced damage. The constructed HA-MNP-DXM NPs had good dispersion, stability, and broad-spectrum scavenging capabilities against multiple reactive free radicals. Moreover, the NPs could be efficiently internalized and exhibited antioxidative, anti-inflammatory, and antiapoptotic effects in CoCl 2 -stimulated renal tubular epithelial NRK-52E cells. Furthermore, the I/R-induced AKI murine model was established to evaluate the in vivo performance of NPs. The results suggested the NPs could specifically target impaired kidneys upon intravenous administration according to NIR-II fluorescence imaging and showed high biosafety. Importantly, the NPs could improve renal function, alleviate oxidative stress and inflammatory reactions, inhibit apoptosis of tubular cells, and restore mitochondrial structure and function, exhibiting excellent therapeutic effects. Further therapeutic mechanism indicated the NPs maintained the cellular/mitochondrial redox balance by modulating the Nrf2 and HO-1 expression. Therefore, the NPs can be a promising therapeutic candidate for the treatment of I/R-induced AKI.
研究领域:
纳米技术
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药学
·
肾脏生理学
·
治疗学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Xiuping Li,Tianyu Cui,Wenxian Zhang,Ziran Zhai,Feixuan Wu,Yuwei Zhang,Mengsu Yang,Wenying Zhong,Wanqing Yue
As one of the biomarkers of liquid biopsy, circulating tumor cells (CTCs) provides important clinical information for cancer diagnosis. However, accurate separation and identification of CTCs remains a great deal of challenge. In present work, we developed novel dopamine-functionalized hyaluronic acid microspheres (HA-DA microspheres) to capture CD44-overexpressing CTCs. The dopamine was grafted onto the hyaluronic acid chain, which was polymerized and cross-linked by oxidation of the catechol groups. Afterwards, a facile microfluidic chip was designed and developed to fabricate the HA-DA microspheres with a diameter of about 45 μm. Our results showed that the CD44+ cells ( i.e. , HeLa, HepG2, A549, MCF-7 and DU-145 cells) could be selectively captured. Then a double-layer microfluidic filter (DLMF) was fabricated for dynamic isolation and detection of CTCs in blood samples. Many slit openings with 15 μm in height were designed to allow white blood cells to clear away, while the microspheres with CTCs were intercepted in the DLMF, which achieved effective separation of CTCs from blood cells. The approach exhibited high capture efficiency even at the cell density as low as 10 cells/mL. We believe the DLMF integrated with HA-DA microspheres could be a promising approach for isolation and detection of CD44-overexpressing CTCs, which is useful for prognosis and early metastasis of cancer patients.
研究领域:
生物医学工程
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肿瘤学
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分子生物学
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微流控技术
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 7
·1-8
·
IF 5.705
Liu Minghuan,Xu Yanan,Huang Chusen,Jia Ti,Zhang Xiaoyan,Yang Da-Peng,Jia Nengqin
A sandwich-type electrochemical cytosensor is described for quantitative determination of CD44-overexpressing HeLa cells. Hyaluronic acid (HA) acts as a targeting molecule that was in-situ incorporated into the sensor based on the use of an indium tin oxide (ITO) electrode modified with multi-walled carbon nanotubes (MWCNTs). The 3D-MWCNT structure is shown to strongly improve the electronic properties and surface chemical reactivities. The HA-modified sensor exhibits a highly sensitive response to HeLa cells. A sandwiched hybridization protocol was then established using BIO [an N-butyl-4-(6′-aminohexyl)amino-1,8-naphthalimide probe modified with HA] as the tracing labels of the fluorescent probes for targeting CD44-positive tumor cells. The signal amplification was thereby maximized and measured by chronocoulometry. The binding of CD44-positive HeLa cells to the HA modified sensing layer causes a decrease in chronocoulometric response. The signal decreases linearly in the 2.1 × 10 2 to 2.1 × 10 7 HeLa cells·mL −1 concentration range with a detection limit of 70 cells·mL −1 . Such a sandwich-type assay may be tailored as a sensitive candidate for detecting low levels of tumor cells.
Schematic of a sandwich cytosensor based on hyaluronic acid-grafted 3D-MWCNT as biosensing interface and BIO as fluorescent probe. This biosensor possessed excellent electrochemical activity, high sensitivity and selectivity, providing a dynamical tracking and detecting platform for CD44-positive tumor cells.
研究领域:
生物医学工程
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癌症检测
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2020
·Vol. 10
·期 3
·2001029
·
IF 7.367
Shuo Huang,Linlin Zhang,Miaomiao Xu,Chao Li,Hongliang Fu,Jie Huang,Xin Jin,Sheng Liang,Hui Wang
New radionuclide-labeled targeting nanocarrier systems have generated new opportunities for tumor treatment and imaging. Nevertheless, such therapeutic strategy is clinically unfeasible on anaplastic thyroid carcinoma (ATC) patients, because of lacking suitable targets and resistance to radiation. In order to figure out a potential treatment, immuno-histochemical staining is performed in human ATC tissue species and high expression of cluster determinant 44 (CD44) is found. Therefore, a CD44-targeted delivery system is designed and constructed by self-assembly of tyrosine (Tyr)–hyaluronic acid (HA)–polyethyleneimine (PEI), which can radiolabel 131/125 I and load a p53 mutant restoring regent, Prima-1. The 125 I-labeled nanocomposites display an impressive tumor imaging as well as a long radiation treatment cycle. The 131 I-labeled nanoparticles show remarkable anti ATC-tumor effects in vitro and in vivo, due to radiosensitization of Prima-1 by reactivation of the p53 mutants.
研究领域:
纳米技术
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肿瘤学
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放射学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yiwen Chen,Zhen Qin,Yujia Wang,Baoxin Gu,Jing Wang,Yunfei Zheng,Yuting Niu,Lingfei Jia
Cancer stem cells (CSCs) play critical roles in tumor growth, metastasis, and chemoresistance. Although several small-molecule inhibitors designed to inhibit CSCs have been investigated in clinical trials, their inadequate tumor targeting and potential off-target side effects have led to poor outcomes. A CD44-targeted virus-mimicking nanomedicine encapsulating the BMI1 inhibitor PTC209 (PTC209@VNP-HA) was designed to treat head and neck squamous cell carcinoma (HNSCC). We used a dendritic mesoporous silica nanoparticle (MSN) as the core for virus-mimicking nanoparticle (VNP) formation after adding shell particles to the MSN surface. The VNP surface was then modified with hyaluronic acid (HA), and PTC209 was adsorbed by mesopores to form PTC209@VNP-HA. In this system, HA is used to target CD44 + CSCs. The rough surface of VNP-HA provided better drug delivery efficiency than smooth nanoparticles modified with HA. VNP-HA enhanced the cancer inhibitory effect of PTC209 12-fold compared to the administration of free PTC209, leading to significantly higher bioavailability of PTC209. Both in vitro and in vivo assays showed that PTC209@VNP-HA inhibited cancer stemness, proliferation, and metastasis in HNSCC. Mechanistically, this inhibitory effect is closely associated with DNA damage/apoptosis signaling. Using a series of preclinical models in murine systems, we confirmed that PTC209@VNP-HA eliminated BMI1 + CSCs, and greatly inhibited the proliferation and metastasis of HNSCC when combined with cisplatin.This study investigated PTC209@VNP-HA as a novel and potentially transformative HNSCC treatment option that eliminates CSCs, prevents metastasis, and overcomes cisplatin resistance.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Fengzhi Qiao,Ya Luo,Peng Lei,Shaolei Wang,Zhi Duan,Hongchang Cui,Tongjie Liu,Huaxi Yi,Cristabelle De Souza,Guanhua Xuan,Xiangzhao Mao,Zhao Ma,Lanwei Zhang,Kai Lin
Probiotics play a crucial role in regulating intestinal immune homeostasis and supporting gut health; however, oral administration faces challenges such as nonspecific distribution and low efficacy. To achieve precise and efficient delivery, in this study, a targeted delivery system embedded probiotics to the colonic inflammatory site CD44 was constructed by covalently linking hyaluronic acid (HA) to cysteine-modified chitosan (CCH) using microfluidic technology. Two probiotic strains, Bifidobacterium bifidum FL-276.1 and Clostridium butyricum ATCC 19398, were encapsulated within the modified chitosan matrix to form probiotics@CCH microspheres (MSs), with an average diameter of approximately 276 μm. Based on the receptor–ligand binding mechanism of HA and CD44, combined with the intestinal mucosal adhesion properties conferred by cysteine-modified chitosan, the probiotics@CCH MSs exhibited a high capture rate for inflammatory Caco-2 cells and demonstrated prolonged retention and targeted localization in a DSS-induced colitis mouse model. Furthermore, probiotics@CCH MSs contributed to maintaining intestinal homeostasis by modulating gut microbiota composition, enhancing short-chain fatty acid production, and supporting the intestinal barrier integrity. The microfluidic-based delivery system facilitates the precise localization of probiotics within the intestine, providing a theoretical basis for enhancing probiotic applications in gut health management.
研究领域:
生物医学工程
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药学
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胃肠病学
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微生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Zongpu Han,Yixiong Lin,Xinyu Guo,Jieyun Xu,Xiaomeng Gao,Ruihan Yang,Yuan Zhao,Mixiao Gui,Linjun Zhang,Yuanlong Guo,Zetao Chen
The strategy of re-organogenesis provides an optimal framework for restoring complex organ structures and functions in adult damage. While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of “Nature selects the fittest to survive” drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance. The extracellular matrix (ECM) serves as the “self-associated molecular patterns” of the niche, containing extensive data on cell-niche reaction data and acting as the active tuner of immune surveillance. In this study, hyaluronic acid (HA) is identified as a unique component of the ECM in cranial osteo-organogenesis. Mechanistically, HA activates the Cluster of Differentiation 44 (CD44)-Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK)-Ets Variant 1/5 (ETV1/5)- Mannose Receptor C-Type 1 (MRC1) axis in macrophages, establishing a distinct immune surveillance during osteo-organogenesis. Furthermore, HA is utilized as a novel engineered material for an “Osteo-organogenesis niche”, restoring immune surveillance and synergistically regulating stem cells to achieve re-osteo-organogenesis in cranial defects of rats. Taken together, the study unveils a previously unknown strategy for leveraging re-organogenesis by utilizing “organogenesis niche” ECM engineered materials to manipulate immune surveillance, thereby comprehensively regulating stem cells and other tissue cells effectively for re-organogenesis.
研究领域:
再生医学
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免疫学
·
组织工程学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Shanshan Sun,Meng Su,Han Xiao,Xiaoshuang Yin,Ying Liu,Wenzhong Yang,Yun Chen
In this study, a self-powered biosensor based on an enzymatic biofuel cell was proposed for the first time for the ultrasensitive detection of soluble CD44 protein. The as-prepared biosensor was composed of the co-exist aptamer and glucose oxidase bioanode and bilirubin oxidase modified biocathode. Initially, the electron transfer from bioanode to biocathode was hindered due to the presence of the aptamer with high insulation, generating a low open-circuit voltage (E OCV ). Once the target CD44 protein was present, it was recognized and captured by the aptamer at the bioanode, thus the interaction between the target CD44 protein and the immobilized aptamer caused the structural change at the surface of the electrode, which facilitated the transfer of electrons. The E OCV showed a good linear relationship with the logarithm of the CD44 protein concentrations in the range of 0.5–1000 ng mL −1 and the detection limit was 0.052 ng mL −1 (S/N = 3). The sensing platform showed excellent anti-interference performance and outstanding stability that maintained over 97% of original E OCV after 15 days. In addition, the relative standard deviation (1.40–1.96%) and recovery (100.23–101.31%) obtained from detecting CD44 protein in real-life blood samples without special pre-treatment indicated that the constructed biosensor had great potential for early cancer diagnosis.
研究领域:
生物化学
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生物传感器
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癌症诊断
·
电化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2015
·Vol. 17
·期 10
·1-10
·
IF 2.184
Chen Daquan,Wang Guohua,Song Weiguo,Zhang Qiang
Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2018
·Vol. 16
·期 1
·1-15
·
IF 5.294
Li Yuanyuan,Shi Sanjun,Ming Yue,Wang Linli,Li Chenwen,Luo Minghe,Li Ziwei,Li Bin,Chen Jianhong
Background Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Results In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice. Conclusions These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
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
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xiaoya Hou,Hua Lin,Xiudi Zhou,Ziting Cheng,Yi Li,Xue Liu,Feng Zhao,Yanping Zhu,Peng Zhang,Daquan Chen
Although the clinical usage of drugs administration was raising, the application of nanoparticles encapsulating the hydrophobic drugs with plummy efficiency was very scarce for atherosclerosis (AS) treatment. In this work, a novel dual ROS-sensitive and CD44 receptors targeting amphiphilic carrier material, oligomeric hyaluronic acid-2′-[propane-2,2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (oHA-TKL-Fc), named HASF, was synthesized and characterized by 1 H-NMR spectra. Then, we combined curcumin (Cur) with HASF into nano-micelles ( [email protected] micelles) by self-assembling method. The resulting [email protected] micelles had the average size of 150.8 nm and zeta potential of -35.04 mV to maintain the will-defined spheroidal structure and stability. Importantly, the [email protected] micelles had ultrahigh entrapment efficiency (about 51.41 %). Moreover, in vitro release study, Cur release from [email protected] micelles was effective in the reactive oxygen species (ROS) condition, and the release rate was interrelated with the concentration of hydrogen peroxide (H 2 O 2 ). Further, fluorescence imaging showed that the [email protected] micelles could more selective access to Raw 264.7 cells than free Cur via oHA-receptor mediated endocytosis. The MTT assay attested the safety of amphiphilic carrier material HASF. Additionally, the results of in vivo Oil red O lipid staining studies showed that the lesion area of the aorta was reduced to 47.3±3.4 % with [email protected] micelles, compared with the lesion area of Cur group (63.2±2.7 %), [email protected] micelles had the more remarkable effect in reducing lesion area (*P < 0.05). Consequently, the novel dual ROS-sensitive and CD44 receptors targeting drug delivery system would become a promising strategy for atherosclerosis.
研究领域:
药学
·
纳米技术
·
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）