BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Jingmou Yu,Yifei Zhang,Meilin Xu,Dengzhao Jiang,Wenbo Liu,Hongguang Jin,Pu Chen,Jing Xu,Lei Zhang
Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.
研究领域:
药剂学
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肿瘤学
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生物材料科学
✓ 已验证
产品关联
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
JOURNAL OF MEMBRANE SCIENCE
·
2025
·
IF 9
Yangyang Li,Riyue Shu,Cheng Zeng,Jing Wang,Lin Zhang,Zhe Tang
The morphological characteristics of tumor cells can provide valuable visual insights into the degree of cell differentiation, which is crucial for accurate cancer grading and diagnosis. The development of biomaterials that can selectively capture these cells while preserving their morphology is essential for advancing cancer diagnosis and treatment. However, designing anti-adhesion biomaterials that possess the ability to capture tumor cells and maintain their structure is still a challenge. Inspired by the dynamic interactions between extracellular matrix and cellular receptors, we propose a versatile nanofibrous membrane functionalized with aptamers and protein binding. Fabricated through a facile polydopamine (PDA) coating on a polyurethane (PU) membrane, this platform provides a bioactive surface for binding functional molecules. The covalent chemistry of PDA allows for the binding of streptavidin (SA) and bovine serum albumin (BSA), forming a highly hydrophilic BSA/SA/PDA@PU membrane. Subsequently, a biotin-modified aptamer (AS1411), which specifically targets tumor cells, were further bound with SA to obtain the AS/BSA/SA/PDA@PU membrane. This modified membrane demonstrates high specificity in capturing tumor cells while preserving cell morphology, providing a promising approach for enhanced cancer diagnostics and therapeutic interventions.
研究领域:
生物材料
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癌症诊断
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细胞生物学
✓ 已验证
产品关联
DOI
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 3.534
Hong Wang,Wanghao Chen,Guojian Wu,Jun Kong,Shaofei Yuan,Lukui Chen
Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe 3 O 4 @T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe 3 O 4 ), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe 3 O 4 @T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe 3 O 4 @T7/AS1411/DTX&SKN-M encapsulated Fe 3 O 4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG 2000 -T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe 3 O 4 @T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe 3 O 4 @T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe 3 O 4 @T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.
研究领域:
药学
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肿瘤学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 60
·34837-34846
·
IF 3.049
Jingjing Li,Qing Li,Meijuan He,Fan Ding,Lulu Cai,Mingming Zhao,Lina Dong,Qi Wang,Kai Xu
With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe nanocarrier has been used phase III trial for cancer treatment. In this study, liposome was employed as a nanocarrier to co-encapsulate MRI nano-contrast agent poly(ethylene glycol)-grafted manganese oxide (PEG-MnO) and anticancer drug paclitaxel (PTX) for the fabrication of a novel theranostic nanocomplex. After being further modified with AS1411 aptamer, the obtained nanoprobe AS1411-liposome-PEG-MnO-PTX displayed the potential of simultaneous MRI diagnosis and therapy of renal carcinoma in vitro and in vivo. It was found that compared with PEG-MnO nano-CA, liposome-PEG-MnO and AS1411-liposome-PEG-MnO presented a stronger MR contrast enhancement effect in the tumor and longer retention time in the tumor region. More importantly, the introduction of AS1411 aptamer further enhanced the MRI effect and the tumor growth inhibition effect, showing its potential use as a theranostic nanoprobe for renal carcinoma.
研究领域:
医学影像学
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Advances
·
2022
·Vol. 4
·期 19
·4059-4065
·
IF 5.598
Lu Zhou,Yajie Zhang,Yong Ma
In recent years, diverse redox-responsive drug delivery systems have emerged to prevent premature drug release and reduce drug toxicity in the human body in cancer treatment. In this paper, we put forward a view of directly utilizing the spatial structure size of the AS1411 aptamer as the nano-gatekeeper on the pore openings of MCM-41 type mesoporous silica and thus constructed a redox-responsive drug delivery system named MCM-41-SS-AS1411. The particles obtained at each step were characterized by TEM, FTIR, SXRD, TGA and zeta potential measurement. The characterization data confirmed that the particles were successfully prepared. The binding amount of the aptamer was ca. 3.1 × 103 for each carrier particle averagely. The anticancer drug Dox was regarded as a drug model to investigate the redox-controlled drug release behavior by fluorescence measurements. The investigation results demonstrate that the spatial volume of aptamer AS1411 can block the mesopore, and this drug-carrier can realize controlled drug release by GSH. We hope this idea can play a prompt role in relevant research. Meanwhile, the preparation steps of this DDS are simplified.
研究领域:
药学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Xiao Liang,Yudi Wang,Hui Shi,Mengmeng Dong,Haobo Han,Quanshun Li
Background Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.
研究领域:
肿瘤学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2019
·Vol. 53
·期 1
·e12713
·
IF 5.039
Tingting Kong,Ronghui Zhou,Yujun Zhang,Liying Hao,Xiaoxiao Cai,Bofeng Zhu
Objectives Carbon dots (CDs), as a fascinating class of fluorescent carbon nanomaterials, have been proven to be powerful tools in the field of bioimaging and biosensing due to their small size, suitable photostability and favourable biocompatibility. However, the cellular uptake of free CDs lacks selectivity and the same negative charges as cell membranes may cause inefficient cell internalization. In this study, an efficient detecting and targeting nanosystem was developed based on the DNA aptamer AS1411 modified CDs with polyethyleneimine (PEI) as connecting bridge. Materials and methods Hydrothermally prepared CDs were assembled with positive-charged PEI, followed by conjugation with AS1411 through electrostatic interaction to form CDs-PEI-AS1411 nanocomplexes. The CDs, CDs-PEI and CDs-PEI-AS1411 were characterized by transmission electron microscopy (TEM), fourier transform infrared (FTIR) spectra, UV–vis spectra, zeta potential measurements and capillary electrophoresis characterizations. The cytotoxicity investigation of the CDs-PEI-AS1411 and CDs-PEI in both MCF-7 and L929 cells was carried out by the CCK-8 assay. The cellular uptake of the CDs-PEI-AS1411 was studied with confocal microscopy and flow cytometry. Results The as-prepared nanosystem possessed good photostability and no obvious cytotoxicity. On the basis of the confocal laser scanning microscope observation and the flow cytometry studies, the cellular uptake of CDs-PEI-AS1411 nanosystem in MCF-7 cells was significantly higher than that of L929 cells, which revealed the highly selective detection ability of nucleolin-positive cells. Conclusions The results of this study indicated that the CDs-PEI-AS1411 nanosystem had a potential value in cancer cell targeted imaging.
研究领域:
纳米技术
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癌症生物学
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生物医学工程
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生物成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2017
·Vol. 19
·期 6
·1-13
·
IF 2.02
Zhang Ran,Wang Shi-Bin,Wu Wen-Guo,Kankala Ranjith Kumar,Chen Ai-Zheng,Liu Yuan-Gang,Fan Jing-Qian
Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly( β -amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents’ doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.
Scheme 1 Schematic illustration of the preparation and cellular uptake of targeted co-delivery system
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
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
·
纳米医学
✓ 已验证
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
·
纳米医学
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材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）