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TALANTA · 2018 · IF 4.244

Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells

Junli Zhang,Xuewei Zhao,Ming Xian,Chuan Dong,Shaomin Shuang

Early diagnosis is pivotal in subsequent prognosis and treatment of cancer. Herein, folic acid-conjugated carbon dots (FA-CDs) as a fluorescent nanoprobe were fabricated for identifying cancer cells visually. Green luminescent carbon dots (CDs) from active dry yeast (ADY) were readily prepared in scale-up to reach macroscopic production with a high yield of ~50% via a facile and rapid microwave approach. The as-prepared CDs were further combined with folic acid (FA) by covalent bonding to fabricate the FA-CDs for identification of cancer cells over-expressing folate receptor (FR). Experimental outcomes demonstrated that the resultant FA-CDs noninvasively entered into cancer cells via receptor-mediated endocytosis and could differentiate FR-positive HepG2 cells from a cell mixture by fluorescence imaging, which suggests a promising prospect of the FA-CDs as an efficient probe for cancer diagnosis and succeeding personalized therapy.

研究领域: 生物医学 · 材料科学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF NANOPARTICLE RESEARCH · 2017 ·Vol. 19 ·期 12 ·1-11 · IF 2.02

Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier

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 · 肿瘤学 · 生物材料学
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CHINESE JOURNAL OF CHEMISTRY · 2013 ·Vol. 31 ·期 8 ·1095-1101 · IF 0.917

A Long-Wavelength Fluorescent Probe for Saccharides Based on Boronic-Acid Receptor

Hongyan Bai,Qian Sun,Haiyu Tian,Junhong Qian,Lingyi Zhang,Weibing Zhang

A single boronic acid-based fluorescent probe (compound CSP) for saccharides was designed and synthesized. The probe, with an α , β -unsaturated ketone conjugated into the coumarin fluorophore, was synthesized by 4 steps from the commercial material 4-diethylamino salicylaldehyde. The electron push-pull effect is enhanced with the N , N -diethyl amino as the electron donor and the carbonyl as the electron acceptor. Both the absorption (463 nm) and emission (616 nm) maxima of CSP are in the visible wavelength region with a Stokes shift of about 150 nm, which ensures CSP a potential probe for biological application. Under near physiological conditions, significant fluorescence enhancement of CSP was observed upon the addition of some saccharides, namely, D -sorbitol, D -fructose, D -glucose, D -mannose and D -galactose. The probe showed relatively high sensitivity towards D -fructose and D -sorbitol, and their detection limits were 0.05 mmol/L and 0.1 mmol/L, respectively.

研究领域: 分析化学 · 生物化学
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Folate receptor targeted bufalin/β-cyclodextrin supramolecular inclusion complex for enhanced solubility and anti-tumor efficiency of bufalin

Aihua Zou,Xiaotong Zhao,Ulrich A. Handge,Vasil M. Garamus,Regine Willumeit-Römer,Peihao Yin

Bufalin (BF), a traditional Chinese medicine, exhibited inhibitory activities against a broad spectrum of tumor cells. The present study elaborates that bufalin was successfully encapsulated into the cavity of β-cyclodextrin (β-CD), which was determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy ( 1 H NMR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The best reaction mole ratio of BF/β-CD was 1:5. The solubilities of bufalin in water and phosphate buffer solution (pH   =   7.4) were increased up to 24 and 34 times after encapsulated into the cavity of β-CD respectively. The inclusion efficiency (IE) and drug loading (DL) of bufalin in the inclusion complex were (94.22   ±   0.85)% and (14.11   ±   0.20)%, respectively. Then β-CD conjugated with folic acid (FA) were further prepared and employed to improve the anti-tumor efficacy of inclusion complex. The in vitro dissolution and solubility study showed better values of inclusion complex and FA targeted inclusion complex than that of pure BF. Cytotoxicity experiments by using HCT116 cell line revealed that the antitumor efficiency of bufalin were enhanced more than two folds in the presence of β-CD and folate conjugated β-CD (FA-PEI-β-CD), which demonstrated the potential application of β-CD (FA-PEI-β-CD) as delivery vehicles of bufalin for antitumor therapy.

CAS / MDL: 9002-98-6 59-30-3
研究领域: 药学 · 肿瘤学 · 生物化学
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International Journal of Nanomedicine · 2022 · IF 7.033

Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging

Nan Ding,Yao Lu,Robert J Lee,Chang Yang,Lei Huang,Jian Liu,Guangya Xiang

Rationale and objective Receptor-targeted delivery of imaging and therapeutic agents can lead to enhanced efficacy for both. Multimodality imaging offers unique advantages over traditional single modality imaging. Tumor marker folate receptor (FR)-targeted fluorescent paramagnetic bimodal liposomes were synthesized to co-deliver paramagnetic and fluorescence agents for magnetic resonance (MR) and optical bimodal imaging contrast enhancement.Materials and methods Fluorescent and paramagnetic bimodal liposomes were synthesized with a mean diameter of 136 nm and a low polydispersity index. The liposomes incorporated folate-PEG3350-CHEMS for FR targeting, Gd(III)[N,N-Bis-stearylamidomethyl-N’-amidomethyl]diethylenetriamine tetraacetic acid (Gd-DTPA-BSA) for MR contrast, and calcein for fluorescence. To determine the specificity and efficiency of delivery, the liposomes were evaluated in FR-positive KB and HeLa cells and FR-negative A549 cells, which were analyzed by fluorescence microscopy, magnetic resonance imaging (MRI), and flow cytometry (FCM).Results FR-specific and efficient cellular uptake of the FR-targeted bimodal liposomes was confirmed by fluorescence microscopy and by FCM. The mean fluorescence intensity (MFI) of KB cells treated with FR-targeted liposomes was 45× that of cells treated with nontargeted liposomes, and 18× that of cells treated with FR-targeted liposomes and excess folic acid (FA). The MFI of HeLa cells treated with targeted liposomes was 33× that of nontargeted liposomes, and was 16× that of the mixture of targeted liposomes and free FA. In contrast, the MFI of A549 cells treated with FR-targeted liposomes was nearly the same as those treated with nontargeted liposomes. The T1-weighted MR images of HeLa and KB cells incubated with FR-targeted liposomes had much higher signal intensity than those treated with nontargeted liposomes or free Gd-DTPA. Furthermore, the FR-targeting effect could be blocked by excess free FA.Conclusion FR-targeted fluorescent paramagnetic bimodal liposomes provided a novel platform for bimodal tumor imaging and theranostic delivery.

研究领域: 医学影像学 · 药剂学 · 肿瘤学
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JOURNAL OF MATERIALS SCIENCE · 2019 ·Vol. 54 ·期 13 ·9707-9717 · IF 3.442

One-step hydrothermal synthesis of ultrabright water-soluble silicon nanoparticles for folate-receptor-mediated bioimaging

Zheng Xiaohui,Zhang Dingfang,Fan Zexuan,Huang Zusheng,Mao Hongju,Ma Yunfei

Fluorescent silicon nanoparticles (SiNPs) exhibiting excellent photostability and colloidal stability and favorable biocompatibility are emerging as novel fluorescent nanoprobes for biological and biomedical imaging. However, studies on the synthesis of highly bright SiNPs and their specific targeted biolabeling are still limited. Herein, we report a facile one-pot hydrothermal approach for the synthesis of ultrabright SiNPs, in which N -[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) molecules and trisodium citrate acted as silicon precursor and reducing agents, respectively. Remarkably, the prepared SiNPs were small (~ 3.5 nm diameter) and showed ultrahigh photoluminescence quantum yield of 85.2% and long-term stability (in pH range of 4–13 and almost saturated NaCl solution, and at 80 °C). The low cytotoxicity of the resultant SiNPs facilitated conjugation with biomolecules such as folic acid (FA) for bioimaging. The FA-conjugated SiNPs specifically bound receptor-positive HepG2 cells over receptor-negative A549 cells, indicating the potential of these SiNPs as robust bioprobe both in vitro and in vivo.

CAS / MDL: 67-68-5 151-21-3 68-04-2
研究领域: 材料科学 · 生物医学 · 纳米技术
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Analytical Methods · 2015 ·Vol. 7 ·期 22 ·9649-9654 · IF 1.821

Mesoporous silica-coated quantum dots functionalized with folic acid for lung cancer cell imaging

Shang Zhou,Danqun Huo,Changjun Hou,Mei Yang,Huanbao Fa,Cui Xia,Mei Chen

The monitoring of folate receptor levels in living cancer cells has attracted increasing interest; however, the present fluorescent probes used often suffer from interference from nonspecific adsorption on the surface of non-target cells. In the present study, the probe is readily prepared by using folic acid as a template molecule, a mesoporous silica nanoparticle as an imprinting material, and a CdTe quantum dot as a signal transducer for the recognition of folate receptors. This system is expected to offer specific recognition of folate receptors over other substances based on the high affinity of folic acid and folate receptors. The probe is stable and monodispersed in an aqueous suspension, and has little toxicity to living cells and thus can be utilized for targeted A549 cell imaging. The living cell imaging experiments further demonstrate its value in bioimaging cell-surface folate receptors by virtue of its superior biocompatibility, lower cytotoxicity and membrane permeability.

研究领域: 生物医学工程 · 纳米医学 · 癌症研究
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NEW JOURNAL OF CHEMISTRY · 2014 ·Vol. 38 ·期 9 ·4519-4526 · IF 3.159

Folate–PEG functionalized silica CdTe quantum dots as fluorescent probes for cancer cell imaging

Miao Lu,Wendian Zhang,Yongkang Gai,Tan Yang,Peng Ye,Guang Yang,Xiang Ma,Guangya Xiang

Fluorescent probes based on quantum dots (QDs) are emerging as ideal tools for sensing and imaging in biological applications owing to their great advantages such as high sensitivity and unique optical properties. Using QDs as potential effective tools for tumor optical imaging would allow early diagnosis, monitoring of tumor progression and treatment efficiency. We prepared a novel folate receptor-targeted, PEG-modified fluorescent probe based on silica-coated CdTe QDs. In the study, the hydrophilic thioglycolic acid stabilized CdTe QDs were directly synthesized in the water phase; the water-in-oil (W/O) reverse microemulsion method was applied to prepare the highly fluorescent amino-functionalized core–shell CdTe@SiO2 particles; subsequently, polyethylene glycol (PEG) and folate molecules were successfully bioconjugated with the CdTe@SiO2 particles through the amino groups. The as-prepared particles were characterized by UV-Vis absorption, fluorescence measurements, particle size, zeta potential and high-resolution transmission electron microscopy (HR-TEM). The bioimaging efficiency and specificity of the prepared fluorescent probes were further evaluated on KB cells. Results indicate that the silica film encapsulated and PEGylated CdTe QDs can significantly reduce the cytotoxicity of CdTe QDs. In conclusion, folate receptor-targeted, PEG-modified and silica-coated CdTe quantum dot fluorescent probes are highly promising for tumor imaging in the near future.

CAS / MDL: 38183-12-9 13494-80-9
研究领域: 生物医学 · 材料科学 · 纳米技术
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Nanoscale Research Letters · 2017 ·Vol. 12 ·期 1 ·1-8 · IF 2.833

Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

Cai Limei,Yu Rufen,Hao Xi,Ding Xiangcui

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

CAS / MDL: 1403-66-3
研究领域: 药剂学 · 肿瘤学 · 生物材料
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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY · 2023 · IF 6.1

Effects of acid acceptor and pH on the structure and filtration performance of nanofiltration membrane

Chenyu Zhu,Xue Zhang,Fuzhi Li,Ruochen Yang,Xuan Zhao

The thin film composite nanofiltration (TFC-NF) membranes with various properties were prepared by changing type and concentration of acid acceptors in the piperazine (PIP) solution. The influences of acid acceptors on interfacial polymerization (IP) process depend on the pH of PIP solution and the properties of acid acceptors. Na 2 CO 3 and TEA provide positive effects at a pH range of 11.2–12.0. Especially for Na 2 CO 3 , water permeability and ion selectivity of the membrane simultaneously enhanced. The pH values reached above 12.8 with NaOH, and negative effects on permeance and selectivity were detected. The pH values ranged 10–11 after adding Na 3 PO 4 and NaHCO 3 . The rejections of both Cl − and SO 4 2− were high, especially for Cl − rejection increasing to above 73%. The pH values got to around 7 with NaH 2 PO 4 . The IP reaction was retarded and defects were detected on the membrane with quite low SO 4 2− rejection. Protonation of PIP happens at low pH, while hydrolysis of acyl chloride of trimesoyl chloride happens at high pH. These changes will slow down the deprotonated PIP diffusion and the IP reaction. It is a feasible way to fabricate tailored NF membranes by changing acid acceptors and adjusting pH value of the PIP solution.

研究领域: 化学工程 · 材料科学 · 环境科学
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JOURNAL OF LUMINESCENCE · 2019 · IF 2.961

Platinated porphyrin tailed with folic acid conjugate for cell-targeted photodynamic activity

Si Yao,Li Chen,Fang Jia,Xinzhi Sun,Huifang Su,Hongjian Liu,Lixia Yang,Zejiang Wang,Fengshou Wu,Kai Wang

For a precisely targeted photosensitizer , we designed and prepared a new platinated porphyrin ( Pt-Por-FA ) by Pt-Por tailed with folic acid ( FA ). The intercalation mode of Pt-Por-FA binding to ct-DNA was confirmed by UV–vis and fluorescent spectra. The singlet oxygen generation of Pt-Por-FA was evaluated through 2′, 7′-dichlorofluorescin (DCFH) method. The cellular uptake and the intracellular localization of Pt-Por-FA were studied upon A549 and HeLa cells through confocal laser scanning microscope. The results showed that the red fluorescence of porphyrin conjugate observed in HeLa cells [folate receptor (FR)–positive] was significantly stronger than that of A549 cells (FR-negative), indicating that Pt-Por-FA could target specifically the cancer cells with overexpression of FR via FR-mediated endocytosis. Pt-Por-FA successfully localized in the lysosomes of cancer cells, but Pt-Por without FA did not. Moreover, the cytotoxicity against HeLa and MDA-MB-231 cells was measured by MTT assay . The results demonstrated that Pt-Por-FA had minor cytotoxicity in the dark, but showed a obviously improving toxicity in presence of light. At the concentration of 20 μM Pt-Por-FA , the cell viabilities were only 12.0% and 26.4% with the IC 50 values down to 5 μm and 12 μm against HeLa and MDA-MB-231 cells, respectively. It suggests that Pt-Por-FA could be a precisely targeted photosensitizer with over-expression of a folate receptor.

研究领域: 药理学 · 肿瘤学 · 生物化学
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NANOTECHNOLOGY · 2014 ·Vol. 25 ·期 23 ·235101 · IF 3.672

‘One-pot’ synthesis of multifunctional GSH–CdTe quantum dots for targeted drug delivery

Xiaoqin Chen,Yajun Tang,Bing Cai,Hongsong Fan

A novel quantum dots-based multifunctional nanovehicle (DOX-QD-PEG-FA) was designed for targeted drug delivery, fluorescent imaging, tracking, and cancer therapy, in which the GSH–CdTe quantum dots play a key role in imaging and drug delivery. To exert curative effects, the antineoplastic drug doxorubicin hydrochloride (DOX) was loaded on the GSH–CdTe quantum dots through a condensation reaction. Meanwhile, a polyethylene glycol (PEG) shell was introduced to wrap the DOX-QD, thus stabilizing the structure and preventing clearance and drug release during systemic circulation. To actively target cancer cells and prevent the nanovehicles from being absorbed by normal cells, the nanoparticles were further decorated with folic acid (FA), allowing them to target HeLa cells that express the FA receptor. The multifunctional DOX-QD-PEG-FA conjugates were simply prepared using the 'one pot' method. In vitro study demonstrated that this simple, multifunctional nanovehicle can deliver DOX to the targeted cancer cells and localize the nanoparticles. After reaching the tumor cells, the FA on the DOX-QD-PEG surface allowed folate receptor recognition and increased the drug concentration to realize a higher curative effect. This novel, multifunctional DOX-QD-PEG-FA system shows great potential for tumor imaging, targeting, and therapy.

CAS / MDL: 24991-53-5
研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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