Journal of Materials Chemistry B
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2022
·Vol. 10
·期 44
·9266-9279
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IF 7.571
Zhihao Guo,Junhui Sui,Yumei Li,Qinchuan Wei,Cailing Wei,Linyun Xiu,Ruohua Zhu,Yong Sun,Jianshe Hu,Ji-Liang Li
Nanotechnology-mediated drug delivery systems suffer from insufficient retention in tumor tissues and unreliable drug release at specific target sites. Herein, we developed an epidermal growth factor receptor-targeted multifunctional micellar nanoplatform (GE11-DOX+CEL-M) by encapsulating celecoxib into polymeric micelles based on the conjugate of GE11-poly(ethylene glycol)-b-poly(trimethylene carbonate) with doxorubicin to suppress tumor growth and metastasis. The polymeric micelles maintained stable nanostructures under physiological conditions but quickly disintegrated in a weakly acidic environment, which is conducive to controlled drug release. Importantly, GE11-DOX+CEL-M micelles effectively delivered the drug combination to tumor sites and enhanced tumor cell uptake through GE11-mediated active tumor targeting. Subsequently, GE11-DOX+CEL-M micelles dissociated in response to intracellular slightly acidic microenvironmental stimuli, resulting in rapid release of celecoxib and doxorubicin to synergistically inhibit the proliferation and migration of tumor cells. Systemic administration of GE11-DOX+CEL-M micelles into mice bearing subcutaneous 4T1 tumor models resulted in higher tumor growth suppression and decreased lung metastasis of tumor cells compared with micelles without GE11 decoration or delivering only doxorubicin. Furthermore, the micelles effectively reduced the systemic toxicity of the chemotherapy drugs. This nanotherapeutic system provides a promising strategy for safe and effective cancer therapy.
研究领域:
纳米医学
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肿瘤学
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药物递送系统
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao
Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.
研究领域:
药学
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免疫学
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癌症研究
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纳米技术
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高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Danrong Hu,Omar Mezghrani,Lei Zhang,Yi Chen,Xue Ke,Tianyuan Ci
Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Fang Nie,Lin Li,Yingying Bai,Jian Yang
Objective Imaging early-stage brain metastases from triple-negative breast cancer (TNBC) is challenging due to the blood–brain barrier (BBB). To address this issue, we developed Den-Angio-GE11, a nanoprobe engineered to traverse the BBB and selectively target metastatic cells.Methods A TNBC brain metastasis model was established in mice through intracardiac injection of MDA-MB-231 brain-seeking cells (MDA-MB-231-BR). Metastatic lesions were longitudinally monitored using T2-weighted magnetic resonance imaging (MRI) and confirmed through contrast-enhanced MRI with Gadolinium-DTPA (Gd-DTPA). The Den-Angio-GE11 nanoprobe was synthesized on a polyamidoamine (PAMAM)-G5 dendrimer platform, incorporating Angiopep-2 and GE11 peptides for BBB traversal and metastatic cell targeting. Dual-modal imaging capability was achieved by conjugating Gd-DTPA for MRI and NIR783 for near-infrared fluorescence (NIRF) imaging.Results Den-Angio-GE11 demonstrated significantly enhanced affinity to EGFR compared to controls, as confirmed by immunofluorescence staining and flow cytometry assays. Brain metastases appeared on T2-weighted MRI three weeks post-injection of MDA-MB-231BR cells and maintained uncompromised BBB function for another one or two weeks, as demonstrated by a lack of enhancement in Gd-DTPA-enhanced MRI. Compared to control nanoparticles, Den-Angio-GE11 remarkably enhanced T1 and NIRF signals of lesions after administration. Histological analysis confirmed Den-Angio-GE11 targeting brain metastatic cells. For lesions in extreme-early stage (undetectable by T2-weighted imaging), NIRF imaging post-Den-Angio-GE11 administration successfully indicated potential lesions. Fluorescence imaging analyses further verified Den-Angio-GE11 targeted sporadically metastatic cells in the brain parenchyma.Conclusion Early brain metastases of TNBC can be detected by Den-Angio-GE11 through T1-weighted MRI or NIRF imaging.
研究领域:
医学影像学
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肿瘤学
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分子生物学
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PubMed
高影响因子
Advanced Healthcare Materials
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2026
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IF 11
Yang Chen,Li Zhu,Wei Xu,Qi Chen,Fei Teng,Kaiwen Bao,Lu Zhang,Yuan Wang,Wei Wu,Zhiqiang Wang
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic options and poor prognosis. To address the shortcomings of conventional therapies, we developed a biomimetic, reactive oxygen species (ROS)-responsive nanoprodrug for synergistic photothermal–chemotherapy of EC. Tannic acid and ellagic acid were chemically linked via boronate ester bonds to form a polyphenol-based nanoparticle (TPE). The epidermal growth factor receptor (EGFR)-targeting peptide GE11 was subsequently introduced onto red blood cell membranes (RBCM) to obtain GE11-RBCM, which was then used to cloak the TPE nanoparticles, yielding GE11-RBCM@TPE. The resulting nanoplatform exhibited excellent photothermal conversion capability under near-infrared irradiation and selectively released the therapeutic payload in response to elevated ROS levels within the tumor microenvironment. In vitro studies showed enhanced cellular uptake in EGFR-overexpressing EC cells and markedly increased cell death following combined photothermal and chemotherapeutic treatment. In vivo, GE11-RBCM@TPE significantly inhibited tumor growth with negligible systemic toxicity and prolonged blood circulation. Transcriptomic analysis further revealed up-regulation of pro-apoptotic ( PER1 , HK2 , BMF , DAPK2 ) and autophagy-related genes ( ATP6V0D2 , HDAC10 , BNIP3 , DEPP1 , ATG9B , NAT16 ), while SQSTM1 and IL6 were down-regulated, indicating simultaneous activation of apoptosis and autophagy. These findings suggest that GE11-RBCM@TPE represents a promising strategy for precise and effective treatment of esophageal cancer.
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高影响因子
Pharmaceutics
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2026
·Vol. 18
·期 4
·498
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IF 6.9
Xingmeng Ma,Zhu Wang,Jingyi Wang,Xingyu Chen,Jinggang Zhang,Dengxue Yang,Shiyi Xu,Xueying Yan
Background/Objective : In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled release of drugs at lung tumor sites through targeted and pH-responsive design. Methods : The GPDD system is formed by the self-assembly of GE11-PEG-hyd-DOX conjugates and co-loads free DOX. This system utilizes the targeting effect of the GE11 peptide with the epidermal growth factor receptor (EGFR) to accumulate at the tumor site, while the hydrazone bond serves as a pH-responsive linker that breaks in the acidic tumor microenvironment, triggering drug release. Experiments employed CCK-8 cytotoxicity assays and tumor-bearing nude mouse models (strain not specified) for in vitro and in vivo evaluations. Results : In vitro experiments showed that GE11-modified GPDD effectively inhibited tumor cell growth. In tumor-bearing nude mouse experiments, GPDD demonstrated more significant tumor suppression effects and lower systemic toxicity compared to free DOX and unmodified PDD. Conclusions : The GPDD nanocarrier integrates targeting and pH responsiveness, improving antitumor efficacy and reducing side effects, with translational potential. The novelty of the study lies in its dual-functional design and co-loading strategy, providing new insights for tumor-targeted delivery systems.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Qinghua Lan,Shuanghu Wang,Zhouming Chen,Junyan Hua,Jieru Hu,Songmei Luo,Yanyan Xu
Galangin (Gal) is a natural plant flavonoid. More and more evidence shows that Gal can achieve anti-tumor effects by regulating various mechanisms. However, its poor water solubility, low bioavailability, and insufficient lesion targeting limit its clinical application. To overcome these shortcomings, we designed and developed a mesoporous nanosystem (GE11-CuS) that actively located the target area and photo-controlled drug release, which promoted the rapid accumulation of drugs in tumor tissues under NIR irradiation, thus achieving positive effects against cancer. In this study, we explored the application of the Gal-loaded nanometer system (GE11-CuS@Gal) in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. The results exhibited that GE11-CuS@Gal had excellent targeting ability and could accumulate efficiently in tumor cells (HSC-3). Meanwhile, the temperature of GE11-CuS@Gal increasing rapidly under NIR illumination damaged the integrity of the carrier and allowed Gal molecules to escape from the pores of the nanoparticles. When the accumulation of Gal in the nidus reached a certain level, the intracellular ROS level could be significantly increased and the antioxidative stress pathway mediated by Nrf2/OH-1 was effectively blocked, to inhibit the growth and migration of tumors. In conclusion, the GE11-CuS improved the antitumor activity of Gal in the body, which laid a foundation for the treatment of OSCC with traditional Chinese medicine ingredients.
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高影响因子
Bioengineering & Translational Medicine
·
2021
·Vol. 7
·期 2
·e10270
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IF 10.711
Chaosheng Yu,Zhen Long,Qianhui Qiu,Fang Liu,Yiming Xu,Tao Zhang,Rui Guo,Wen Zhong,Shuixian Huang,Shuaijun Chen
One of the main clinical treatments for advanced nasopharyngeal carcinoma is chemotherapy, but systemic administration can cause serious adverse reactions. New type of nanomaterial which can actively targeting, imaging, and treating nasopharyngeal carcinoma at the same time to enhance the effect of chemotherapy, meanwhile monitoring the intracellular drug release process at the level of single cancer cell was urgently needed. GE11, an EGFR antagonist peptide, was used to target nasopharyngeal carcinoma which has positive expression of EGFR on its nucleus. GE11-modified graphene quantum dots (GQDs@GE11) were used as drug carriers for clinical chemotherapeutics cisplatin (CDDP) and doxorubicin (DOX). The emission spectrum of GQDs (460 nm) and the excitation spectrum of DOX (470 nm) have a good overlap, thus the transfer and release process of DOX can be sensitively detected by the fluorescence resonance energy transfer (FRET). CDDP was used to enhance the chemotherapy effect of nanoprobe, and the loading amount of DOX and CDDP on GQDs@GE11 nanoprobe were up to 67 and 50 mg/g, respectively. In vivo experiments have confirmed that GQDs@GE11/CDDP/DOX nanoprobe can be enriched to tumor site through specific targeting effect, and significantly inhibit tumor cell proliferation. This new type of targeted therapy fluorescent probe provides new ideas for the study of drug release process and the treatment of nasopharyngeal carcinoma.
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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生物医学工程
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高影响因子
ACS Nano
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2024
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IF 15.8
Weiran Cao,Xue Zhang,Yaxuan Feng,Rui Li,An Lu,Zijie Li,Fei Yu,Lu Sun,Jiancheng Wang,Zhiyu Wang,Huining He
Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role in maintaining intracellular redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due to rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing their cytotoxicity and rendering them less effective. In this study, we combined erastin, a GSH biosynthesis inhibitor, with 2′-deoxy-5-fluorouridine 5′-monophosphate sodium salt (FdUMP), an ROS-based drug, to effectively disrupt intracellular redox homeostasis and reverse chemotherapy resistance. Therefore, efficient ferroptosis and apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, we employed small interfering RNA targeting PD-L1 (siPD-L1) as a third agent to block immune-checkpoint recognition by CD8+ T cells. The highly immunogenic cell peroxidates or damage-associated molecular patterns (DAMPs) induced by erastin acted synergistically with downregulated PD-L1 to enhance the antitumor effects. To codeliver these three drugs simultaneously and efficiently, we designed GE11 peptide-modified lipid nanoparticles (LNPs) containing calcium phosphate cores to achieve high encapsulation efficiencies. In vitro studies verified its enhanced cytotoxicity, efficient intracellular ROS induction and GSH/GPX4 downregulation, substantial lipid peroxidation product accumulation, and mitochondrial depolarization. In vivo, this formulation effectively accumulated at tumor sites and achieved significant tumor inhibition in subcutaneous colon cancer (CRC) mouse models with a maximum tumor inhibition rate of 83.89% at a relatively low dose. Overall, a strategy to overcome clinical drug resistance was verified in this study by depleting GSH and activating adaptive immunity.
研究领域:
癌症生物学
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药学
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纳米技术
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免疫学
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分子生物学
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PubMed
高影响因子
ACS Nano
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2025
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IF 16
Lianxue Zhang,Yun Teng,Hai Yang,Jianxiang Huang,Zhaoqi Shi,Cenhao Wu,Zaixing Yang,Liquan Huang,Jun Zou,Ruhong Zhou
Chordoma presents a formidable therapeutic challenge due to its distinct anatomical location, thus complicating its complete surgical resection coupled with marked resistance to both radiotherapy and chemotherapy. Currently, effective systemic therapies remain unavailable, contributing to a poor prognosis for patients. To address this critical unmet need, we have developed a targeted drug delivery system tailored to the tumor biology of chordoma. This system encapsulates the CDK7 inhibitor THZ1 within nanoparticles featuring diselenide bonds as dual-responsive release triggers. Upon exposure to low-dose X-ray irradiation (e.g., 2 Gy) and to the elevated reactive oxygen species (ROS) level in the tumor microenvironment, these diselenide bonds are cleaved and transformed into selenic acid (RSeOOH), which subsequently initiates rapid carrier disassembly and drug release. The synergy between RSeOOH and THZ1 enhances radiotherapy efficacy by modulating p53 signaling, inducing apoptosis, and promoting G2/M phase cell cycle arrest in U-CH1 cells, thereby overcoming the radiotherapy resistance commonly seen in chordoma. To further improve tumor-specificity, we functionalize the carrier with the EGFR-targeting GE11 peptide, which drives selective drug accumulation at tumor sites. In murine models, this delivery system has demonstrated substantial efficacy in combination with radiochemotherapy and yet produces minimal toxicity. Molecular dynamics simulations have further elucidated carrier self-assembly mechanisms, guiding the rational design of this nanoplatform.
研究领域:
纳米医学
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肿瘤学
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放射治疗学
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药理学
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生物化学
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生物物理学
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材料科学
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高影响因子
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