Nanomaterials
·
2022
·Vol. 12
·期 4
·696
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IF 5.719
Chao Zhang,Shuangqing Fu,Fanghua Zhang,Mengnan Han,Xuming Wang,Jie Du,Honglei Zhang,Wei Li
Combination chemotherapy is emerging as an important strategy for cancer treatment with decreased side effects. However, chemotherapeutic drugs with different solubility are not easy to realize co-delivery in traditional nanocarriers. Herein, an affibody modified G-quadruplex DNA micellar prodrug (affi-F/GQs) of hydrophilic 5-fluorodeoxyuridine (FUdR) by integrating polymeric FUdRs into DNA strands is developed for the first time. To achieve synergistic efficacy with hydrophobic drugs, curcumin (Cur) is co-loaded into affi-F/GQs micelles to prepare the dual drug-loaded DNA micelles ([email protected]/GQs), in which affibody is employed as a targeting moiety to facilitate HER2 receptor-mediated uptake.[email protected]/GQs have a small size of approximately 130 nm and exhibit excellent stability. The system co-delivers FUdR and Cur in a ratiometric manner, and the drug loading rates are 21.1% and 5.6%, respectively. Compared with the physical combination of FUdR and Cur,[email protected]/GQs show higher cytotoxicity and greater synergistic effect on HER2 positive gastric cancer N87 cells. Surprisingly,[email protected]/GQs significantly enhance the expression and activity of apoptosis-associated proteins in Bcl-2/Bax-caspase 8, 9-caspase 3 apoptotic pathway, which is the main factor in the death of tumor cells induced by FUdR. Overall, this nanoencapsulation is a promising candidate for the targeted co-delivery of drugs with significant differences in solubility.Keywords:G-quadruplex;DNA micelles;affibody;5-fluorodeoxyuridine;curcumin;synergetic therapy
研究领域:
癌症治疗
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纳米技术
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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
Theranostics
·
2015
·
IF 8.022
Li Ding,Caiping Tian,Song Feng,Guissi Fida,Congying Zhang,Yuxiang Ma,Guanhua Ai,Samuel Achilefu,Yueqing Gu
Targeting tumors using miniature antibodies is a novel and attractive therapeutic approach, as these biomolecules exhibit low immunogenicity, rapid clearance, and high targeting specificity. However, most of the small-sized antibodies in existence do not exhibit marked anti-tumor effects, which limit their use in targeted cancer immunotherapy. To overcome this difficulty in targeting multiple biomarkers by combination therapies, we designed a new bifunctional antibody, named MaAbNA (multivalent antibody comprised of nanobody and affibody moieties), capable of targeting EGFR1 and HER2, which are widely overexpressed in a variety of tumor types. The small-sized (29 kDa) MaAbNA, which was expressed in E.coli , consists of one anti-EGFR1 nanobody and two anti-HER2 affibodies, and possesses high affinity (K D ) for EGFR1 (~4.1 nM) and HER2 (~4.7 nM). In order to enhance its anti-tumor activity, MaAbNA was conjugated with adriamycin (ADM) using a PEG2000 linker, forming a new complex anticancer drug, MaAbNA-PEG2000-ADM. MaAbNA exhibited high inhibitory effects on tumor cells over-expressing both EGFR1 and HER2, but displayed minimal cytotoxicity in cells expressing low levels of EGFR1 and HER2. Moreover, MaAbNA-PEG2000-ADM displayed increased tumoricidal effects than ADM or MaAbNA alone, as well exhibited greater antitumor efficacy than EGFR1 (Cetuximab) and HER2 (Herceptin) antibody drugs. The ability of MaAbNA to regulate expression of downstream oncogenes c-jun, c-fos, c-myc, as well as AEG-1 for therapeutic potential was evaluated by qPCR and western-blot analyses. The antitumor efficacy of MaAbNA and its derivative MaAbNA-PEG2000-ADM were validated in vivo , highlighting the potential for use of MaAbNA as a highly tumor-specific dual molecular imaging probe and targeted cancer therapeutic.
研究领域:
肿瘤学
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药理学
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生物技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-14
·
IF 3.998
Zhang Chao,Zhang Fanghua,Han Mengnan,Wang Xuming,Du Jie,Zhang Honglei,Li Wei
Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2 + cancer.
研究领域:
癌症研究
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纳米技术
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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
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-23
·
IF 10.435
Wang Haijun,Jia Dianlong,Yuan Dandan,Yin Xiaolei,Yuan Fengjiao,Wang Feifei,Shi Wenna,Li Hui,Zhu Li-Min,Fan Qing
Background Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O 2 production, which in turn serves as a “radiosensitizer” to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. Results Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (Z Her2 ) mediated cisplatin-loaded mesoporous polydopamine/MnO 2 /polydopamine nanoparticles (Pt@mPDA/MnO 2 /PDA-Z Her2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O 2 . Z Her2 , produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T 1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of Z Her2 . These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. Conclusions The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics. Graphic abstract
研究领域:
纳米医学
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癌症治疗
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分子生物学
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生物医学工程
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放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xinyu Zhang,Hui Liu,Chenyu Wang,Yuan Gao,Shiqi Zhao,Mengyao Mu,Ke Ren,Yufang Gong,Qing Fan,Xiao Sun
Biodegradable Two-dimensional (2D) nanomaterials have attracted tremendous interest in biomedical application. Herein, a biodegradable ferrous sulfide nanosheet with ultrathin structure and uniform size was developed. Following its development, the application of the self-enhanced photothermal nanoplatform (FMPN) in vivo by combining Mn-DOTA and dimeric PD-L1 affibody for targeted dual-mode magnetic resonance imaging (MRI) guided synergistic tumor therapy is explored. Dual-contrast enhanced subtraction imaging (DESI) was used to evaluate the excellent T1-T2 MRI ability of FMPN. FMPN displayed excellent photothermal conversion efficiency (η = 40.33 %) and biodegradability, thus had good tumor photothermal therapy effects with good biosafety. In addition, FMPN with pH-responsive Fe 2+ release can effectively induce tumor cell ferroptosis, further intensifying PTT and subsequent immunologic cell death. PD-L1 affibody could endow this nanoplatform with efficient tumor targeting, terminating T cells’ immune suppression by effectively blocking the interaction between PD-1 and PD-L1. Systemic delivery of FMPN significantly inhibited tumor progression in primary, metastatic and abscopal tumors, and showed obvious dual-mode MRI enhancement. Therefore, this nanoplatform exhibited promising potential for MRI-guided synergistic ferroptosis/photothermal/immunotherapy.
研究领域:
纳米技术
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生物医学工程
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肿瘤学
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分子影像
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诊疗一体化
✓ 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）