RSC Advances
·
2015
·Vol. 5
·期 94
·77204-77210
·
IF 3.84
Yue Dai,Aiping Zhang,Jia You,Jingjing Li,Huiting Xu,Kai Xu
Magnetic resonance imaging (MRI) as a noninvasive diagnostic technology with high spatial resolution has been widely used in clinics. However, the relatively low sensitivity is the main shortcoming of this technology. To address this issue, we would like to develop a molecular MRI nanoprobe for the sensitive and specific MRI of renal carcinoma cells with BSA-Gd2O3 nanoparticles as MRI contrast agents, mesoporous silica nanoparticles (mSiO2 NPs) as nanocarriers and the AS1411 aptamer as a targeting molecule. To achieve this aim, BSA-Gd2O3 NPs were assembled onto mSiO2 NPs with the help of anionic polyelectrolyte, sodium polystyrene sulfonate (PSS), and cationic polyelectrolyte, poly dimethyl diallyl ammonium chloride (PDDA) layer by layer. Such successful assembly was confirmed by transmission electron microscopy (TEM), FT-IR spectroscopy, zeta-potential analysis, hydrodynamic diameter determination and gel electrophoresis. After assembly, the mSiO2/PSS/PDDA/BSA-Gd2O3 nanoprobe presented a larger longitudinal relaxivity (r1) (26.1 s−1 mM−1 Gd) than BSA-Gd2O3 NPs (11.8 s−1 mM−1 Gd) and commercially used Gd–DTPA (3.87 s−1 mM−1 Gd). Additionally, with the AS1411 aptamer as a targeting molecule, our fabricated mSiO2/PSS/PDDA/BSA-Gd2O3-AS1411 nanoprobes could recognize clear cell renal carcinoma cells (ccRCC) specifically by MRI in vitro.
研究领域:
医学影像
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纳米技术
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癌症研究
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材料科学
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产品关联
DOI
高影响因子
Molecular Therapy-Nucleic Acids
·
2025
·
IF 6.1
Shaowen Yang,Chengwen Zheng,Sixuan Cheng,Li Wen,Pinghui Li,Jianbo Li,Xiaoli Lan,Dawei Jiang
Aptamers are single-stranded oligonucleotides with specific spatial structures. They have been widely used in preclinical studies because of their high affinity and specificity for various biological targets. AS1411, an aptamer targeting the nucleolin overexpressed on the cancer cell membrane, is one of the most promising and extensively studied aptamers. However, extremely low bioavailability due to rapid renal excretion remains a great obstacle for aptamers’ clinical translation. Human serum albumin (HSA), with long blood circulation and excellent biocompatibility, has been an attractive vehicle for extending drugs’ blood half-life in the clinic. This work investigated the effect of an albumin-conjugated strategy in improving aptamers’ tumor targeting in vivo for the first time by taking AS1411 as an example. HSA-AS1411 was synthesized via the maleimide-sulfhydryl reaction. The excellent serum stability and maintained target affinity of HSA-AS1411 were demonstrated in vitro . The pharmacokinetic analysis and tumor SPECT imaging studies revealed that HSA-AS1411 had over 14 times longer circulation half-life and superior tumor uptake than those of AS1411. The immunofluorescence staining of tumor tissues further indicated the improved tumor retention of AS1411 as a result of prolonged blood circulation. Therefore, the HSA-conjugated strategy has a promising prospect in improving aptamers’ tumor targeting for clinical applications.
研究领域:
药理学
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分子生物学
·
肿瘤学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2015
·
IF 5.636
Yan-Ran Li,Qian Liu,Zhangyong Hong,He-Fang Wang
For the widely used “off-on” fluorescence (or phosphorescence) resonance energy transfer (FRET or PRET) system, the separation of donors and acceptors species was vital for enhancing the sensitivity. To date, separation of free donors from FRET/PRET inhibition systems was somewhat not convenient, whereas separation of the target-induced far-between acceptors has hardly been reported yet. We presented here a novel magnetic separation-assistant fluorescence resonance energy transfer (MS-FRET) inhibition strategy for highly sensitive detection of nucleolin using Cy5.5-AS1411 as the donor and Fe3O4-polypyrrole core–shell (Fe3O4@PPY) nanoparticles as the NIR quenching acceptor. Due to hydrophobic interaction and π–π stacking of AS1411 and PPY, Cy5.5-AS1411 was bound onto the surface of Fe3O4@PPY, resulting in 90% of fluorescence quenching of Cy5.5-AS1411. Owing to the much stronger specific interaction of AS1411 and nucleolin, the presence of nucleolin could take Cy5.5-AS1411 apart from Fe3O4@PPY and restore the fluorescence of Cy5.5-AS1411. The superparamagnetism of Fe3O4@PPY enabled all separations and fluorescence measurements complete in the same quartz cell, and thus allowed the convenient but accurate comparison of the sensitivity and fluorescence recovery in the cases of separation or nonseparation. Compared to nonseparation FRET inhibition, the separation of free Cy5.5-AS1411 from Cy5.5-AS1411-Fe3O4@PPY solution (the first magnetic separation, MS-1) had as high as 25-fold enhancement of the sensitivity, whereas further separation of the nucleolin-inducing far-between Fe3O4@PPY from the FRET inhibition solution (the second magnetic separation, MS-2) could further enhance the sensitivity to 35-fold. Finally, the MS-FRET inhibition assay displayed the linear range of 0.625–27.5 μg L–1 (8.1–359 pM) and detection limit of 0.04 μg L–1 (0.05 pM) of nucleolin. The fluorescence intensity recovery (the percentage ratio of the final restoring fluorescence intensity to the quenched fluorescence intensity of Cy5.5-AS1411 solution by 0.09 g L–1 Fe3O4@PPY) was enhanced from 36% (for nonseparation) to 56% (for two magnetic separations). This is the first accurate evaluation for the effect of separating donor/acceptor species on the FRET inhibition assay.
研究领域:
生物化学
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分析化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Liping Dong,Wenzhuo Ran,Yanqiong Li,Lixia Yang,Xi Zhou
Realgar (As 4 S 4 ) has shown antitumor activity, but its pharmaceutical application is limited by poor aqueous solubility, low bioavailability, and systemic toxicity. In this study, we developed AS1411-functionalized albumin nanoparticles (As 4 S 4 @ BSA-AS1411 NPs) for targeted delivery of realgar to triple-negative breast cancer (TNBC). Bulk As 4 S 4 was converted into nanosized clusters and encapsulated in a bovine serum albumin (BSA) matrix, followed by surface conjugation with the nucleolin-targeting aptamer AS1411. The resulting nanoparticles showed suitable physicochemical properties and good colloidal stability in physiologically relevant media, together with enhanced cellular internalization in 4T1 cells. Compared with non-targeted nanoparticles, AS1411 modification significantly increased cytotoxicity and reduced the migratory ability of 4T1 cells. Mechanistic studies showed that treatment with As 4 S 4 @BSA-AS1411 NPs was associated with upregulation of GADD45G and downregulation of mTOR, suggesting a stress-related antiproliferative effect. In vivo fluorescence imaging demonstrated increased tumor accumulation of AS1411-functionalized NPs. In 4T1 tumor-bearing mice, systemic administration of As 4 S 4 @BSA-AS1411 NPs produced greater tumor growth inhibition than non-targeted controls, accompanied by increased apoptosis and reduced proliferative activity in tumor tissues. In addition, the formulation showed good in vivo tolerability, with no evident systemic toxicity or hemolytic activity. These findings indicate that AS1411-functionalized albumin NPs are a promising delivery system for improving the antitumor efficacy and safety profile of realgar in TNBC.
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Mengyue Li,Hanxi Zhang,Peizheng Xiong,Yuhan He,Wanyi Zhou,Chunhui Wu,Xiaoling Liao,Wei Zhang,Hong Yang,Yiyao Liu
Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells. Moreover, the sandwich cavity spatially protects siPD-L1 from degradation, and the featured design of the DNA/RNA duplex linkers ensures effective intracellular release of siPD-L1. The pH-responsive release of cytotoxic DOX induces apoptosis and initial mild immunogenic cell death of tumor cells, presenting antigens to enhance the maturation of dendritic cells (DCs) with the assistance of the immune adjuvant CpG, thereby activating cytotoxic T lymphocytes to amplify antitumor immunity. Simultaneously, siPD-L1 downregulated the endogenous expression of PD-L1 to inhibit adaptive tumor immune escape. DSWAC/siPD-L1 initiated the iterative revolution of the cancer-immunity cycle, leading to the inhibition of primary and metastatic tumors, as demonstrated by DC maturation and T-cell infiltration in established subcutaneous primary tumor model and metastatic lung tumor model. Furthermore, the superior antitumor effect of DSWAC/siPD-L1 resulted in approximately 91 % inhibition of primary tumor growth and 93 % prevention of lung metastasis. Collectively, this study describes a siPD-L1-based sandwich DNA nanodevice functionalized with AS1411/CpG for enhanced cancer chemo-immunotherapy, inspiring the creation of more innovative drug nanocarriers and the exploitation of novel cancer therapies.
研究领域:
纳米医学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2026
·
IF 4.1
Zheng Sihong,Zhang Ren,Zhang Wenjia,Su Ning,Gao Mingxia,Zhang Xiangmin
Surface-enhanced Raman scattering (SERS) technology has attracted increasing attention in the field of biological imaging. Herein, we designed a new biomimetic SERS nanoprobe by sequentially modifying 4-mercaptobenzonitrile (4-MBN), cell membrane (CM), and AS1411 aptamer on the gold nanostars (Au@MBN@CM@apt) for synergistic targeted imaging of tumor cells. The Au@MBN@CM@apt probe integrates the distinctive functional properties of its constituent components. The internal gold nanostars (AuNS) with multi-tip structure significantly enhance the signal of Raman reporter molecules. Raman reporter molecule 4-MBN is adsorbed on the surface of AuNS, and its cyano group yields a characteristic Raman peak at 2226 cm −1 , within Raman silent region, thereby minimizing the interference from endogenous biomolecules. Encapsulation with cell membrane endows the nanoprobes with excellent stability and biocompatibility, thus reducing phagocytosis and clearance by macrophages. Moreover, the incorporation of AS1411 aptamers into the cell membrane enables specific recognition of nucleolin, a protein overexpressed in various cancer cell types. With these merits, the designed Au@MBN@CM@apt nanoprobes exhibit distinct SERS signals in the Raman silent region, free from interference by endogenous biomolecules, and maintain good stability, with retained signal stability for up to 170 days. These characteristics render them suitable for the targeted detection and SERS imaging of nucleolin-overexpressing cancer cells, using MCF-7 cells as the model, against normal cells. Furthermore, the Au@MBN@CM@apt nanoprobes generates signals in the Raman silent region, thereby effectively avoiding spectral overlap with intrinsic tissue components. As a result, they were successfully used for SERS imaging of tissue sections, allowing high-contrast delineation of tumor tissue margins with results consistent with hematoxylin and eosin (H&E) staining. Collectively, these findings demonstrate that our work holds significant promise for background-free tumor visualization. Graphical abstract
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 5
·304
·
IF 5.4
Xiong Nuoxuan,Lin Yue,Luo Fang,Lin Cuiying,Qiu Bin,Lin Zhenyu,Jiang Zhou,Wang Jian
Nucleolin (NCL) is a critical biomarker for early cancer diagnosis and prognostic evaluation. To overcome the limitations of existing detection methods, such as insufficient sensitivity and cumbersome procedures, this study reports an ultrasensitive biosensing platform based on an organic photoelectrochemical transistor (OPECT). The biosensor employs a guanine-rich DNA aptamer, AS1411, immobilized on an n-GaN/Au gate electrode. Specific binding to NCL induces AS1411 to fold into a G-quadruplex (G4) structure, whose intrinsic π-π stacking interactions are proposed to establish an efficient charge transport channel. This effect substantially promotes the separation of photogenerated holes, and combining this with the intrinsic gain of the OPECT transconductance mechanism yields notable signal amplification. As a result, the proposed sensor exhibits ultrahigh sensitivity with a limit of detection (LOD) of 0.28 pM (S/ N = 3) and a wide linear range from 1 pM to 100 nM. The excellent analytical performance originates from the synergistic effect of OPECT amplification, G4-mediated charge transport, efficient photoelectric conversion of the GaN/Au gate, and minimal signal loss. Moreover, the biosensor demonstrates high selectivity against potential interfering proteins and reliable quantitative accuracy in complex biological matrices. In the analysis of breast cancer cell lysates, recoveries range from 96.4% to 97.6%, consistent with the standard ELISA method. This work establishes a label-free detection strategy wherein ultrasensitive signal transduction is achieved exclusively through aptamer conformational switching-without requiring heterojunction engineering enabling point-of-care NCL analysis. Graphical
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Qiantong Liu,Dongming Liu,Ji Wen,Li Yang
To address the limitations of single therapy and ensure the safe and efficient delivery of nanomedicine, we developed carbon/manganese nanoparticles (NPs). These NPs were engineered by depositing manganese dioxide on the surface of mesoporous carbon (MMCN), thus enabling Peroxidase (POD)-Catalase (CAT)-Glutathione peroxidase (GPX)-like function. Following the modification with AS1411 aptamer (AMMCN), doxorubicin hydrochloride (DOX) was incorporated to produce AMMCN@DOX. This compound demonstrated satisfactory biocompatibility, efficient tumor tissue accumulation, and the capability to release DOX in response to the tumor microenvironment (TME). It was confirmed that AMMCN@DOX is effectively endocytosed by cells, releases DOX, decomposes H 2 O 2 to generate O 2 to alleviate tumor hypoxia, and mediates a Fenton-like reaction. Additionally, AMMCN@DOX showed excellent photothermal conversion efficiency, producing localized heating in tumors and yielding superior synergistic anti-tumor activity in mice with solid tumors. Thus, this study proposes a safe, targeted delivery strategy for carbon/manganese NPs, facilitating chemical, chemokinetic, and photothermal synergistic therapy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 47
·7898-7907
·
IF 4.776
Qiu-ge Zhao,Jing Wang,Yu-peng Zhang,Jing Zhang,An-na Tang,De-ming Kong
To overcome the side effects caused by premature drug leakage from carriers and to achieve more efficient cancer treatment via the synergy of photodynamic therapy (PDT) and chemotherapy, a porphyrinic metal–organic framework (porMOF)-based drug delivery system (ZnO-gated porMOF-AS1411) was prepared and its ability to efficiently deliver small molecule drugs was tested. In this system, the porous porMOF plays the dual roles of a PDT photosensitizer and a drug carrier. To overcome premature drug leakage and thus reduce side effects and improve drug delivery efficiency, pH-sensitive ZnO nanoparticles were used to cover the porMOF nanopores. Neutral and alkaline pH-stable ZnO ensured that the loaded drugs were encapsulated in the porMOF pores during delivery. However, ZnO disintegration in the acidic lysosomal environment opened the pores, permitting drug release. Further assembly of nucleolin-specific AS1411 aptamers conferred the nanosystem with target-specific recognition and accumulation abilities. In this work, we demonstrated that the proposed nanosystem could be successfully used to efficiently deliver, with controllable release, the chemotherapeutic drug doxorubicin (DOX), thus achieving bimodal cancer treatment by PDT and chemotherapy. In vitro and in vivo experiments demonstrated that this synergistic therapeutic modality achieved highly efficient cancer cell-killing and tumor ablation without undesirable side effects.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Bo Chen,Linrui Cai,Rangrang Fan,Min Mu,Di Chuan,Yangmei Ren,Haifeng Chen,Gang Guo
Photodynamic therapy (PDT) as emerging phototherapy has attracted extensive attention in cancer therapy. However, the overexpressed glutathione (GSH) and hypoxic conditions of the tumor microenvironment (TME) sevely limit the therapeutic efficiency of PDT. Herein, we design a multifunctional nanoplatform (CBDM) for cancer therapy consisting of photosensitizer (Ce6), bovine serum albumin (BSA), and polydopamine-manganese dioxide (MnO 2 ) nanocomplex, which is simultaneously modified by nucleolin-targeting AS1411 aptamer. This MnO 2 -based nanoplatform ameliorates tumor hypoxia and promotes oxygen production via the reaction between MnO 2 and endogenous H 2 O 2 and acid H + in the TME. Besides, this biocompatibility nanoplatform exhibits an augmented PDT effect and high photothermal conversion efficiency under 808 nm laser irradiation. Importantly, the MnO 2 -based nanoplatform achieves a significant in vivo synergistic therapeutic effect and fights against liver metastasis of breast cancer. As a result, the excellent biocompatibility, especially the superior anticancer efficacy, and suppression of tumor metastasis make the MnO 2 -based nanoplatform a promising candidate for cancer therapy.
研究领域:
癌症治疗
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纳米医学
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Yang Yuming,Han Yu,Sun Qiuyang,Cheng Jin,Yue Caixia,Liu Yanlei,Song Jie,Jin Weilin,Ding Xianting,de la Fuente Jesús M.,Ni Jian,Wang Xiaoqiang,Cui Daxiang
Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.Conclusion sThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
研究领域:
纳米技术
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肿瘤学
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药学
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分子医学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Xuling Chen,Jianbo Ji,Ke Zhou,Xiaohui Fan,Lingbing Li,Wei Xu
Despite its high antitumor activity , the clinical application of chemotherapy is greatly impeded by lacking of specific accumulation and poor solubility. To address the above challenges, we designed a AS1411 aptamer modified nanoparticles based on molecular recognition of nucleobases . Firstly, a redox sensitive Paclitaxel-SS-Zidovudine (PZ) prodrug was synthesized. Then PZ/β-lapachone/AS1411/DSPE-PEG nanoparticles were prepared and AS1411 aptamer was connected through molecular recognition between the nucleoside analogue Zidovudine (ZDV) and the thymine on aptamer. DSPE-PEG (DP) was incorporated into nanoparticles to prolong the residence time of nanoparticles in the blood circulation . Furthermore, to realize the combination treatment, β-lapachone (LAP) has been incorporated into nanoparticles with high drug loading efficiency through the interaction of π-π stacking force and H-bonding between LAP and Paclitaxel (PTX). LAP can generate abundant exogenous reactive oxygen species (ROS) via the bioactivation of NAD(P)H: quinone oxidoreductase-1 (NQO1). Moreover, the connection of Zidovudine (ZDV) and AS1411 through molecular recognition of nucleobases further optimized the nanoparticles with high affinity to nucleolin which overexpressed on tumor cell membrane , thereby inducing the specific accumulation of nanoparticles in tumor sites. In vivo and in vitro studies showed that the obtained nanoparticles of PZ/LAP/AS1411/DP exhibited better tumor growth inhibition and lower systemic side effects. Herein, we have rationally conducted a novel self-codelivery system for effectively synergistic antitumor treatment.
研究领域:
药理学
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纳米技术
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癌症研究
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）