BIOMACROMOLECULES
·
2024
·
IF 5.5
Qingrong Li,Xiaoyuan Yang,Xuelin Xia,Xiao-Xia Xia,Deyue Yan
Recombinant elastin-like polypeptides (ELPs) have emerged as an attractive nanoplatform for drug delivery due to their tunable genetically encoded sequence, biocompatibility, and stimuli-responsive self-assembly behaviors. Here, we designed and biosynthesized an HER2 (human epidermal growth factor receptor 2)-targeted affibody–ELP fusion protein (Z-ELP), which was subsequently conjugated with monomethyl auristatin E (MMAE) to build a protein–drug conjugate (Z-ELP-M). Due to its thermal response, Z-ELP-M can immediately self-assemble into a nanomicelle at physiological temperature. Benefiting from its active targeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization and deep tumor penetration in vitro. Moreover, Z-ELP-M shows excellent tumor targeting and superior antitumor efficacy in HER2-positive ovarian cancer, demonstrating a relative tumor growth inhibition of 104.6%. These findings suggest that an affibody-functionalized elastin-like peptide–drug conjugate nanomicelle is an efficient strategy to improve antitumor efficacy and biosafety in cancer therapy.
研究领域:
生物医学工程
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Xiaomeng Lu,Xinyu Zhan,Guozi Xia,Feifei Wang,Mingjia Lv,Renwei Liu,Yuxue Liu,Chen Zi,Guangyong Li,Rui Wang,Jun Li,Fengjiao Yuan,Dianlong Jia
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive candidate for anticancer therapeutics due to its efficient pro-apoptotic activity against tumor cells and its well-tolerated safety profile. However, the in vivo antitumor efficacy of TRAIL is often limited by its poor tumor targeting capacity. Nowadays, the B7 homologue 3 (B7–H3) immune checkpoint has emerged as a promising target for tumor immunotherapy and drug delivery. Here, we report the achievement of tumor-targeted delivery of TRAIL by genetically fusing it with a B7H3-antagonistic affibody. The affibody–TRAIL fusion protein, named ACT, was easily expressed in Escherichia coli with a high yield and could form the active trimeric state. In vitro ACT showed significantly increased cellular binding to multiple B7H3-positive tumor cells and improved cytotoxicity by 2–3 times compared to the parent TRAIL. In vivo ACT demonstrated a 2.4-fold higher tumor uptake than TRAIL in mice bearing B7H3-positive A431 tumor grafts. More importantly, ACT exhibited significantly improved antitumor efficacy against tumors in vivo. In addition, ACT treatment did not cause body weight loss or histopathological changes in the major organs of mice, indicating its good safety profile. Overall, our findings demonstrate that targeting B7H3 to enhance TRAIL delivery is a viable approach to improve its therapeutic efficacy, and ACT may be a potential agent for targeted therapy of B7H3-positive tumors.
研究领域:
肿瘤学
·
免疫治疗
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 32
·期 20
·205103
·
IF 3.874
Ran Sun,Yuyang Zhao,Yanan Wang,Qian Zhang,Ping Zhao
Dual-modal molecular imaging that combines photoacoustic imaging with near-infrared fluorescence imaging integrates the benefits of both imaging modalities and may achieve more precise detection of disease. In this study, silver sulfide quantum dots (Ag2S QDs) with superior photoacoustic properties and a strong fluorescent emission in the NIR region were successfully synthesized. They were further modified with the insulin-like growth factor 1 receptor (IGF-1R) targeted small scaffold protein, Affibody (ZIGF-1) to achieved targeted photoacoustic/fluorescent dual-modal imaging of cancer. Our results showed that the prepared nanoprobe had good tumor targeting properties in vivo, and the probe also showed good biocompatibility without any significant toxicity.
研究领域:
生物医学工程
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癌症研究
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分子成像
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纳米技术
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生物相容性
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 4
·1982-1989
·
IF 3.049
Chao Zhang,HongLei Zhang,MengNan Han,XueLi Yang,ChaoHong Pei,ZhiDong Xu,Jie Du,Wei Li,Shengxi Chen
Cisplatin is the most widely used anticancer drug, but its side effects limit the maximum systemic dose. To circumvent the side effects, a DNA tetrahedron–affibody nanoparticle was prepared by combination of a DNA chain with cisplatin via interstrand crosslinks or adducts. Each nanocarrier can bind ∼68 molecules of cisplatin. This cisplatin nanoparticle exhibited high selectivity and inhibition for breast cancer HER2 overexpressing cells BT474 and lower toxicity in MCF-7 cells with low HER2 expression. The nano-drug inhibited the growth of BT474 cells by 94.57% at 512 nM (containing 33.3 μM cisplatin), which was higher than that of cisplatin (82.9%, 33.3 μM).
研究领域:
肿瘤学
·
分子生物学
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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 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
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 35
·16581-16590
·
IF 7.233
Ying Zhang,Ning Zhao,Yeshan Qin,Fengxia Wu,Zhihua Xu,Tian Lan,Zhen Cheng,Ping Zhao,Hongguang Liu
Photoacoustic imaging (PAI) is a new and attractive imaging modality, and it has strong potential for application in the early detection of tumors through the use of optically absorbing targeted contrast agents. Ag2S quantum dots (QD) are a promising bionanomaterial and have attracted significant attention in the field of bioimaging. In this study, water-soluble and carboxylic acid group-coated Ag2S QDs with an ultrasmall size (∼8 nm) were synthesized via a one-step method. Their surface plasmon resonance wavelength was determined to be ∼800 nm, which is ideal for PAI. Ag2S QDs were then modified with the epidermal growth factor receptor 1 (EGFR) targeted small protein affibody ZEGFR:1907. The resulted nanoprobe, ZEGFR:1907-Ag2S QDs, was then used for targeted PAI of EGFR-overexpressed tumors. The biodistribution of the nanoprobe was further measured by ex vivo near infrared fluorescence (NIRF) imaging of the dissected tissues. The PAI results showed that ZEGFR:1907-Ag2S QDs specifically image EGFR positive tumors. The biodistribution study revealed that the nanoprobe mainly accumulated in the liver, spleen and tumors; tissue H&E staining studies indicated that the probe has good biocompatibility. Overall, the affibody-functionalized Ag2S QDs are a novel targeted nanoprobe that can be used for specific PAI of tumors.
研究领域:
生物医学工程
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纳米技术
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癌症研究
·
分子影像
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 3.534
Dianlong Jia,Feifei Wang,Yujiao Yang,Ping Hu,Hao Song,Yue Lu,Rui Wang,Guangyong Li,Renmin Liu,Jun Li,Fengjiao Yuan
Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (Z EGFR ) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR + A431 tumor cells in vitro and in vivo . The LS-DDP coupled with Z EGFR (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro , AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 μg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 μg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of Z EGFR . In vivo , the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with Z EGFR enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR + tumors.
研究领域:
肿瘤学
·
药学
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分子生物学
·
药物递送系统
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Xiaoyuan Yang,Xuelin Xia,Xiao-Xia Xia,Zhao Sun,Deyue Yan
Tumor necrosis factor-related apoptosis ligand (TRAIL) is a promising protein candidate for selective apoptosis of a variety of cancer cells. However, the short half-life and a lack of targeted delivery are major obstacles for its application in cancer therapy. Here, we propose a simple strategy to solve the targeting problem by genetically fusing an anti-HER2 affibody to the C-terminus of the TRAIL. The fusion protein TRAIL-affibody was produced as a soluble form with high yield in recombinant Escherichia coli. In vitro studies proved that the affibody domain promoted the cellular uptake of the fusion protein in the HER2 overexpressed SKOV-3 cells and improved its apoptosis-inducing ability. In addition, the fusion protein exhibited higher accumulation at the tumor site and greater antitumor effect than those of TRAIL in vivo, indicating that the affibody promoted the tumor homing of the TRAIL and then improved the therapeutic efficacy. Importantly, repeated injection of high-dose TRAIL-affibody showed no obvious toxicity in mice. These results demonstrated that the engineered TRAIL-affibody is promising to be a highly tumor-specific and targeted cancer therapeutic agent.
研究领域:
生物技术
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Dianlong Jia,Yujiao Yang,Fengjiao Yuan,Qing Fan,Feifei Wang,Yujiao Huang,Hao Song,Ping Hu,Rui Wang,Guangyong Li,Renmin Liu,Jun Li
Epidermal growth factor receptor (EGFR) is overexpressed in a wide range of solid tumors . In this study, we exploited a high-affinity EGFR-antagonistic affibody (Z EGFR ) coupled to a doxorubicin loaded pegylated liposome (LS-Dox) for concurrent passive and active targeting of EGFR + A431 tumor cells in vitro and in vivo . The in vitro studies revealed that the Dox liposomes coupled with Z EGFR (AS-Dox) showed a higher Dox uptake than LS-Dox in EGFR + A431 cells but not in EGFR − B16F10 cells, resulting in a selectively enhanced cytotoxicity. In vivo , AS-Dox confirmed its long circulation time and efficient accumulation in tumors. This targeted chemotherapy achieved greater tumor suppression. Further, this low-dose but effective targeted treatment reduced systemic toxicity such as body weight loss and organ injury demonstrated by H&E staining. Thus, selective targeting of LS-Dox coupled with Z EGFR enhanced antitumor effects and improved systemic safety. These results demonstrated that LS-Dox coupled with Z EGFR might be developed as a potential tool for therapy of EGFR + tumors.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chao Zhang,Mengnan Han,Fanghua Zhang,Xueli Yang,Jie Du,Honglei Zhang,Wei Li,Shengxi Chen
Background Chemotherapy, as an adjuvant treatment strategy for HER2-positive breast cancer, can effectively improve clinical symptoms and overcome the drug resistance of therapeutic monoclonal antibodies. Nucleoside analogues are a class of traditional chemotherapeutic drugs that are widely applied in adjuvant therapy. However, there are many critical issues that limit their clinical efficiency, including poor selectivity and stability, severe side effects and suboptimal therapeutic efficacy. Hence, this work aims to develop a new DNA nanocarrier for targeted drug delivery to solve the above problems.Methods Four 41-mer DNA strands were synthesized and 10 FUdR molecules were attached to 5ʹ end of each DNA strand by DNA solid-phase synthesis. An affibody molecule was connected to the end of polymeric FUdR through a linker in one of the four strands. The affibody-FUdR-tetrahedral DNA nanostructures (affi-F/TDNs) were self-assembled through four DNA strands, in which one vertex was connected to an affibody at the end of a polymeric FUdR tail and three vertices were only polymeric FUdR tails. In vitro cellular uptake of affi-F/TDNs was examined visually with confocal fluorescence microscopy and flow cytometry, and the cytotoxicity of affi-F/TDNs against cancer cells was investigated with MTT assay. Cell apoptosis was detected by Annexin V-FITC/PI double staining method. Using NOD/SCID (Mus Musculus) mice model, the targeted killing efficacy of affi-F/TDNs was also evaluated.Results The drug-loading of FUdR in affi-TDNs was 19.6% in mole ratio. The in vitro results showed that affi-F/TDNs had high selectivity and inhibition (81.2%) for breast cancer BT474 cells overexpressing HER2 and low toxicity in MCF-7 cells with low HER2 expression. During the in vivo application, affi-F/TDNs displayed good stability in the blood circulation, achieved specific accumulation in tumor region and the best antitumor efficacy (inhibition ratio of 58.1%), and showed excellent biocompatibility.Conclusions The affibody-DNA tetrahedrons, as a simple and effective active targeting delivery nanocarrier, provided a new avenue for the transport of nucleoside antitumor drugs.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Yuliang Sun,Wenlong Zhang,Yilin Lu,Yanan He,Badrul Yahaya,Yanli Liu,Juntang Lin
In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSC intelligent ) that endows the carrier platform with “wisdom” by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSC intelligent with tumor signal recognition capacity, so that MSC intelligent can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSC intelligent can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSC intelligent under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSC intelligent without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSC intelligent is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.
研究领域:
癌症生物学
·
纳米技术
·
分子生物学
·
干细胞研究
·
生物医学工程
✓ 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
·
生物医学工程
·
肿瘤学
·
分子影像
·
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）