JOURNAL OF NANOPARTICLE RESEARCH
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2017
·Vol. 19
·期 9
·1-11
·
IF 2.02
Zhou Shang,Huo Danqun,Hou Changjun,Yang Mei,Fa Huanbao
The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor (~8–9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy.
• Hyaluronan functionalizing sulfhydryl chitosan-coated CdTe QDs were designed as a “turn-on” fluorescence probe for recognizing cancer cells. • The fabricating probe is based on the high affinity of hyaluronan and CD44 receptor for specific recognition of CD44 receptor in lung cancer cell. • The probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. • The probe showed the lower background signal than that of always-on nanoprobes avoiding the non-specific adsorption on the surface of the normal cells.
研究领域:
生物医学工程
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分子生物学
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癌症研究
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Chunting Li,Jiexuan Wang,Xinmiao Lu,Huang Ge,Xin Jin,Qinhua Guan,Yue su,Ruijun Pan,Peiyong Li,Wei Cai,Xinyuan Zhu
Circulating tumor cells (CTCs) represent the most common way of tumor metastasis and has been considered as a significant index for tumor diagnosis, staging and prognosis. However, CTC detection and analysis are always limited by the scarcity of CTC in the peripheral blood and the interference of blood cells. Therefore, here we presented with a hydrogen peroxide (H 2 O 2 )–response nanoprobes with CD44-targeted ability to reduce the interference of blood cells and improve the detection efficiency and accuracy and the pancreatic cancer cell was used to evaluate the feasibility of our probe. Shortly, hydrophobic H 2 O 2 -response naphthalimide-borate fluorophore was introduced onto the hydrophilic hyaluronic acid to form an amphiphilic complex, which could self-assemble into fluorescent nanoprobes in water. Our studies demonstrated that the nanoprobes were not only able to specifically recognize the pancreatic cancer cells with overexpressed CD44 proteins and reduce the influence of white blood cells in the peripheral blood, but also capable of semi-quantifying H 2 O 2 content in CTCs, Which could be further used as a significant index for tumor clinical evaluation and therapy.
研究领域:
肿瘤学
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医学诊断
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2017
·Vol. 19
·期 12
·1-11
·
IF 2.02
Chen Daquan,Song Xiaoyan,Wang Kaili,Guo Chunjing,Yu Yueming,Fan Huaying,Zhao Feng
In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance ( 1 H–NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential − 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.
研究领域:
药学
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肿瘤学
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生物材料学
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-14
·
IF 10.6
Luo Wenqi,Li Yueying,Zhao Jianhui,Niu Renrui,Xiang Chunyu,Zhang Mingyu,Xiao Chunsheng,Liu Wanguo,Gu Rui
Background Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery.Results The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI.Conclusion sThese results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.
研究领域:
神经科学
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纳米医学
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药理学
✓ 已验证
DOI
高影响因子
Nanoscale Research Letters
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2018
·Vol. 13
·期 1
·1-10
·
IF 3.125
Wang Kaili,Qi Mengjiao,Guo Chunjing,Yu Yueming,Wang Bingjie,Fang Lei,Liu Mengna,Wang Zhen,Fan Xinxin,Chen Daquan
In this work, novel mitochondrial and CD44 receptor dual-targeting redox-sensitive multifunctional nanoparticles (micelles) based on oligomeric hyaluronic acid (oHA) were proposed. The amphiphilic nanocarrier was prepared by (5-carboxypentyl)triphenylphosphonium bromide (TPP), oligomeric hyaluronic acid (oHA), disulfide bond, and curcumin (Cur), named as TPP-oHA-S-S-Cur. The TPP targeted the mitochondria, the antitumor drug Cur served as a hydrophobic core, the CD44 receptor targeting oHA worked as a hydrophilic shell, and the disulfide bond acted as a connecting arm. The chemical structure of TPP-oHA-S-S-Cur was characterized by 1 HNMR technology. Cur was loaded into the TPP-oHA-S-S-Cur micelles by self-assembly. Some properties, including the preparation of micelles, morphology, redox sensitivity, and mitochondrial targeting, were studied. The results showed that TPP-oHA-S-S-Cur micelles had a mean diameter of 122.4 ± 23.4 nm, zeta potential − 26.55 ± 4.99 mV. In vitro release study and cellular uptake test showed that TPP-oHA-S-S-Cur micelles had redox sensibility, dual targeting to mitochondrial and CD44 receptor. This work provided a promising smart multifunctional nanocarrier platform to enhance the solubility, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs.
研究领域:
药剂学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Yishun Yang,Yuan Zhao,Jinshuai Lan,Yanan Kang,Tong Zhang,Yue Ding,Xinyu Zhang,Lu Lu
Introduction A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. Materials and methods HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. Results DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (−6.7 to −31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 μg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. Conclusion HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Qi Chen,Xiaorong Li,Yuan Xie,Weicheng Hu,Zhipeng Cheng,Hui Zhong,Hongjun Zhu
Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co -assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2021
·
IF 3.383
Xiaoyun Mo,Fuling Wu,Ying Li,Xiulan Cai
Chemotherapeutic drug has inevitable drawbacks of nonspecific tumor targeting and poor therapeutic efficiency, limiting practical clinical applications. To overcome these challenges, a novel halloysite nanotube-based drug delivery system was designed for efficient CD44-mediated targeting in this study. CD44 molecule, a major receptor for hyaluronic acid (HA), overexpressed in aggressive cancer cells. The successful synthesis of hyaluronic acid modified halloysite (HNTs-NH-HA) complexes were proved by 13 C solid state NMR spectroscopy , FT-IR, XPS and TGA. Thereafter, a model anticancer drug doxorubicin (DOX) was loaded into HNTs-NH-HA to from the final drug delivery system (HNTs-NH-HA/DOX). In vitro cytotoxicity assay tests revealed that HNTs-NH-HA/DOX improved therapeutic efficacy of DOX by specific targeting. Furthermore, confocal laser scanning microscopy (CLSM) results showed better uptake of HNTs-NH-HA/DOX nanoparticles in CD44 receptor-positive cells than in CD44 receptor-negative cells. It was expected that HNTs-NH-HA drug delivery systems hold great potential for targeting CD44 over-expressing tumors.
研究领域:
纳米技术
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药学
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癌症研究
·
材料科学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Jianping Li,Man Li,Lifeng Tian,Yue Qiu,Qianwen Yu,Xuhui Wang,Rong Guo,Qin He
A facile approach was developed to synthesize an innovative hyaluronic acid-modified carbon dot-doxorubicin nanoparticles drug delivery platform. CD44 targeted HA-modified carbon dots (HA-CDs) were synthesized as carrier by one-step hydrothermal treatment within one hour with citric acid and branch-PEI as core carbon source. HA not only functioned as carbon dot component but also as hydrophilic group and targeting ligand of this system. The as-prepared HA-CDs were then loaded with doxorubicin (HA-CD@p-CBA-DOX) via an acid-cleavable bond, which released drug in a pH-responsive manner. In in vitro experiments, HA-CD@p-CBA-DOX displayed good hemocompatibility and serum stability, while exhibited high cytotoxicity on 4T1 cells. The confocal laser scanning microscopy and flow cytometry results demonstrated that DOX-loaded nanoparticles were internalized by 4T1 cells via HA-mediated CD44-targeting effect. The enhanced in vivo tumor accumulation of HA-CD@p-CBA-DOX was testified by live imaging. Compared with free DOX, superior in vivo anti-tumor efficacy of HA-CD@p-CBA-DOX was observed in both heterotopic and orthotopic 4T1 cell tumor models. Furthermore, blood hematology and blood biochemistry analysis demonstrated that HA-CD@p-CBA-DOX did not induce noticeable toxicity, which further confirmed the good biocompatibility of HA-CD@p-CBA-DOX. The formulated HA-CD@p-CBA-DOX provides an alternative strategy for targeted breast cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2023
·Vol. 42
·期 1
·1-13
·
IF 11.3
Liu Ruolan,Li Qiong,Qin Siyuan,Qiao Ling,Yang Mei,Liu Shanshan,Nice Edouard C.,Zhang Wei,Huang Canhua,Zheng Shaojiang,Gao Wei
Background Lung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency. Methods Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo. Results Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects. Conclusions Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Shuaishuai Feng,Zi-Xin Wu,Ziyan Zhao,Jinhu Liu,Kaoxiang Sun,Chuanyou Guo,Hongbo Wang,Zimei Wu
This study aimed to develop an efficient step-by-step osteosarcoma (OS)-targeting liposome system functionalized with a redox-cleavable, bone- and cluster of differentiation 44 (CD44)-dual-targeting polymer. Furthermore, the effect of coadministration of a tumor-penetrating peptide, internalizing RGD (iRGD), was investigated. First, a bone-targeting moiety, alendronate (ALN), was conjugated with hyaluronic acid (HA), a ligand for CD44. This ALN–HA conjugate was coupled with DSPE–PEG2000–COOH through a bioreducible disulfide linker (−SS−) to obtain a functionalized lipid, ALN–HA–SS–L, to be postinserted into preformed liposomes loaded with doxorubicin (DOX). The roles of ALN, HA, and the redox sensitivity of the ALN–HA–SS–L liposomes (ALN–HA–SS–L–L) in the anti-OS effect were critically evaluated against various reference liposomal formulations (with only ALN, HA, or redox sensitivity). ALN–HA–SS–L–L displayed a zeta potential of −26.07 ± 0.32 mV and selectively disassembled in the presence of a reducing agent, 10 mM glutathione, which can be found in cancer cells. Compared to various reference liposomes, ALN–HA–SS–L–L/DOX had significantly higher cytotoxicity to human OS MG-63 cells alongside high and rapid cellular uptake. In the orthotopic OS nude mouse models, ALN–HA–SS–L–L/DOX showed remarkable tumor growth suppression and prolonged survival time. This result was further improved by the coadministration of iRGD. The antitumor effects of various liposomes were ranked in the same order as the degree of tumor biodistribution shown by in vivo/ex vivo imaging: ALN–HA–SS–L–L coadministered with iRGD > ALN–HA–SS–L–L > HA–SS–L–L > HA–L–L > PEG–L> free drug. ALN–HA–SS–L–L/DOX also reduced the cardiotoxicity of DOX and lung metastases. Overall, this study demonstrated that ALN–HA–SS–L–L/DOX, equipped with bone- and CD44-dual-targeting abilities and redox sensitivity, could be a promising OS-targeted therapy. The efficacy could also be augmented by coadministration of iRGD.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Mengna Liu,Bingjie Wang,Chunjing Guo,Xiaoya Hou,Ziting Cheng,Daquan Chen
In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 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）