STAR Protocols
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2023
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IF 0
Yunfei Yi,Chan Feng,Mian Yu,Lin Mei,Meiying Wu,Wei Tao
Summary Efficient gene delivery in an integrated drug delivery system is urgent for multimodal antitumor therapy. Herein, we describe a protocol for constructing a peptide-based siRNA delivery system to achieve tumor vascular normalization and gene silencing in 4T1 cells. We highlighted four major steps, including (1) synthesis of the chimeric peptide, (2) preparation and characterization of P A7R @siRNA micelleplexes, (3) in vitro tube formation assay and transwell cell migration assay, and (4) siRNA transfection in 4T1 cells. This delivery system is expected to be used to silence gene expression, normalize tumor vasculature, and perform other treatments based on the different peptide segments. For complete details on the use and execution of this protocol, please refer to Yi et al. (2022). 1
研究领域:
癌症生物学
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分子生物学
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药学
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生物技术
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DOI
PubMed
International Journal of Nanomedicine
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2025
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IF 6.5
Xiaoyan Yuan,Yunfeng Bi,Ji Liu,Wenhao Xu,Mingjuan Li,Kexin Li,Yan Zou,Xing Wang,Yanqing Chen,Qiming Yang
Objective Andrographolide (AG) demonstrated promising anticancer efficacy against the initiation and progression of breast cancer by triggering the mitochondria-mediated intrinsic apoptotic pathway. However, its clinical translation is still hindered by drawbacks such as poor bioavailability and off-target effects; therefore, an optimized drug-delivery system that minimizes these effects is urgently needed. To address these issues, we successfully developed a mitochondria-targeting nanocarrier (TPP-PEG-PCL) with high drug-loading capacity and excellent biocompatibility.Methods The mitochondria-targeting copolymer (TPP-PEG-PCL) was synthesized chemically and used to prepare AG-loaded polymeric micelles (TPP-PEG-PCL@AG) by solvent-evaporation method. In vitro, the blank micelles were first evaluated for biocompatibility with mouse breast-cancer cells (4T1) and endothelial cells (EC). Subsequently, a panel of cellular assays was performed on 4T1 cells to compare the antitumor activity of free AG, PEG-PCL@AG, and TPP-PEG-PCL@AG, confirming the enhanced cancer-cell killing achieved through mitochondria-targeted delivery of AG.Results The results showed that TPP-PEG-PCL micelles were readily taken up by 4T1 cells and selectively accumulated in mitochondria with a Pearson’s correlation (Rr) 0.47 compared to 0.25 in PEG-PCL micelles group, leading to a pronounced inhibition of proliferation and migration. By elevating intracellular ROS, decreasing mitochondrial membrane potential, and activating the caspase cascade, the micelles induced apoptosis and thereby achieved mitochondria-targeted potentiation of TPP-PEG-PCL@AG. However, this study is limited to in vitro validation using the 4T1 murine model, and further in vivo investigations are warranted to assess translational efficacy and potential systemic toxicity..Conclusion PCL-PEG nanoparticles decorated with TPP combine pronounced mitochondria-targeting specificity, high drug-loading capacity, excellent biocompatibility and readily tunable architecture, making them an ideal platform for constructing a precise mitochondrial-intervention system for AG. This strategy is particularly attractive for tumor-targeted delivery of AG and opens a new avenue for its clinical translation.
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PubMed
高影响因子
Nanoscale
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2019
·Vol. 12
·期 3
·1801-1810
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IF 6.97
Yang Gao,Luyun Zhang,Yanhong Liu,Sijia Sun,Zhibin Yin,Lili Zhang,Aiguo Li,Guangming Lu,Aiguo Wu,Leyong Zeng
Black titanium dioxide (TiO2) nanoparticles have attracted great attention due to their application in photothermal therapy (PTT). However, single-mode phototherapy has the risk of recurrence, and the high-dose laser usually imposed to improve the PTT performance can bring a potential threat to security. Here, polydopamine (PDA)-coated black TiO2 (b-P25@PDA) nanoparticles with a core–shell structure were synthesized for enhanced PTT; then, synergistic phototherapy nanoprobes (b-P25@PDA-Ce6 (Mn)) were constructed by coupling chlorin e6 (Ce6) and chelating Mn2+ for simultaneous photodynamic therapy (PDT)/PTT and magnetic resonance (MR) imaging, in which a low-dose laser was used and imaging-guided phototherapy with high efficiency and high safety was achieved. The prepared nanoprobes showed high photothermal conversion efficiency (32.12%), high reactive oxygen generation and excellent MR imaging. In the 4T1 tumor-bearing nude mouse model, the tumors completely disappeared under the combination of PDT/PTT with a low-dose laser but were only partially inhibited by single PDT and single PTT. The current work developed a multifunctional black TiO2-based nanoprobe for enhanced synergistic PDT/PTT and MR imaging, which will be important for the safe and efficient visualized theranostics of cancers.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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医学成像
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PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Yuqin Yang,Desheng Cai,Yisong Shu,Zhihua Yuan,Wenmin Pi,Yaozhi Zhang,Jihui Lu,Jingyi Jiao,Xuehao Cheng,Feifei Li,Penglong Wang,Haimin Lei
It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos -glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg −1 , and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.
研究领域:
肿瘤学
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药学
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分子生物学
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癌症治疗
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DOI
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Tingting Gong,Xiaohuan Wang,Ziqi Liu,Pengxin Li,Yunqian Lu,Yaoyao Guo,Meihua Han,Xiangtao Wang
A significant obstacle in oncological therapy lies in surmounting the immunosuppressive microenvironment while enhancing the anti-tumor efficacy of chemotherapeutic agents. STING agonists such as Mn 2+ have demonstrated substantial promise in this regard. Squamocin (Squ), a naturally derived compound, exhibits potent anti-tumor activity with minimal drug resistance; however, its application is hampered by poor water solubility (approximately 7.5 μg/mL) and off-target toxicity. In this study, a chemo-immunotherapy approach utilizing MnO 2 nanoparticles combined with squamocin (Squ) has been formulated, with its therapeutic effectiveness further augmented through surface modification with the tumor-targeting IR820 molecule. The intravenously injectable MnO 2 nanoparticles were synthesized from KMnO 4 and anhydrous ethanol, and subsequently modified with Astragalus polysaccharides (APS)-IR820 on their surface to improve stability in physiological media and facilitate tumor targeting and in vivo fluorescence imaging. The resultant MnO 2 @APS-IR820 NPs, measuring 193.4 ± 1.7 nm, generated Mn 2+ in response to the elevated glutathione (GSH) levels within the tumor microenvironment. The generated Mn 2+ notably induced maturation of bone marrow dendritic cells (BMDCs) and promoted the repolarization of tumor-associated macrophages from the pro-tumor M2 phenotype to the anti-tumor M1 phenotype. When combined with Squ@APS-IR820 NPs (220.1 ± 11.2 nm in size), the chemoimmunotherapy significantly stimulated both innate and adaptive immune responses in a 4T1 tumor bearing mouse model and demonstrated a synergistic anti-tumor effect, achieving a tumor inhibition rate of approximately 92%, highlighting its remarkable potential for anti-tumor therapy.
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-15
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IF 9.429
Liu Xiang-Yu,Zhu Mao-Hua,Wang Xiao-Yu,Dong Xiao,Liu Hai-Jun,Li Rui-Yang,Jia Shi-Chong,Lu Qin,Zhao Mei,Sun Peng,Chen Hong-Zhuan,Fang Chao
Background Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy. Methods NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG 5000 , which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated. Results Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG 5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice. Conclusions The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy. Graphical Abstract
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
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肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2021
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IF 6.244
Li Xiaoyu,Xia Shujun,Ji Ri,Zhan Weiwei,Zhou Wei
Objectives: A novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation.Methods: VEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs.Results: The average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was −13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated.Conclusion: Nano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.
研究领域:
医学影像学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2026
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IF 4.9
Fangzhou Yang,Yunqian Lu,Xiaoxue Lang,Lina Sun,Hang Zou,Ziting Zhou,Yaoyao Guo,Yifei Guo,Xiangtao Wang,Meihua Han
Whole cells serve as promising carriers for delivering bioactive molecules owing to their superior biocompatibility, minimal immunogenicity, and extended circulation time. In addition to preserving the intact cellular structure and functions, they provide abundant tumor-associated antigens as immune targets, providing a basis for tumor vaccine development. However, conventional chemotherapy with doxorubicin (DOX) suffers from limited tumor-targeting ability and severe systemic toxicity, which markedly restrict its therapeutic efficacy. In this study, we establish a simple liquid nitrogen freezing strategy to load DOX into liquid-nitrogen-treated (LNT) tumor cells for homologous targeting of breast cancer. The optimized formulation achieved a DOX loading of 38.28 ± 1.61 μg/5 × 106 cells. Both in vitro and in vivo studies confirm that the prepared DOX/LNT cell formulation exhibits excellent safety with no proliferative or pathogenic potential. Regarding the antitumor effect of DOX/LNT cells, in vitro cytotoxicity assays reveal an IC50 value of 1.104 μg/mL, representing a 1.87-fold improvement over free DOX. Furthermore, DOX/LNT cell achieves superior antitumor efficacy by combining chemotherapy with the activation of antitumor immune responses. Following intravenous administration via tail vein injection, in vivo studies demonstrated a tumor inhibition rate of 81.81%, extending the average survival time of breast tumor-bearing mice to 56 days. This approach offers a novel drug delivery system with improved tumor-targeting specificity, representing a precise and effective therapeutic strategy that integrates chemotherapy and immunotherapy for breast cancer treatment.
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高影响因子
Toxicology Research
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2024
·Vol. 13
·期 1
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IF 2.2
Zhang Chu,Liao Yupei,Li Tangjia,Zhong Haijing,Shan Luchen,Yu Pei,Xia Chenglai,Xu Lipeng
The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.
研究领域:
肿瘤学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Zhengyue Kang,Min Yang,Xiaoling Feng,Hongjian Liao,Zhifei Zhang,Yonghong Du
Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.
研究领域:
肿瘤学
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纳米技术
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医学影像
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癌症治疗
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生物医学工程
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DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Kan He,Xia Meng,Jinxing Su,Shangquan Jiang,Min Chu,Bei Huang
The therapeutic mechanism of oleanolic acid (OA) in breast cancer has been widely reported, but little has been known about the combined effects of transcriptome and gut microbiome. In this study, the phenotypic effect of oleanolic acid on mice was tested at the end of the administration cycle, and RNA sequencing on murine tumor tissue and 16S-rRNA sequencing on intestinal contents were conducted to analyze gene expression profiles and microbial diversity between the control group and OA treated group using 4T1-induced mice breast cancer model. As a result, it has been confirmed that oleanolic acid would play a significant inhibitory effect on the development of breast tumors in mice. Based on the integrative analysis of the transcriptomic and metagenomic data, it was found that the abundance of Lactobacillus in the intestinal flora of mice significantly increased in the OA group. Moreover, the up-regulation of Il10 had a significant effect on inhibiting the tumor progression, which played a role through cytokine-cytokine receptor interaction pathway.
研究领域:
肿瘤学
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微生物组学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
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IF 5.162
Dinglingge Cao,Huangjuan Li,Yuan Luo,Nianping Feng,Tianyuan Ci
Phototherapy holds promise in cancer treatment for its prominent antitumor efficacy and low systematic toxicity compared with traditional chemotherapy. However, the higher risk of tumor metastasis caused by the severe hypoxic state during phototherapy is a threat in practical use. Here, in order to tackle this challenge, we developed a delivery system via loading the photosensitizer indocyanine green (ICG) into the low molecular weight heparin (LMWH) modified liposomes (LMWH-ICG-Lip) to realize the synergistic effects between photosensitizer and drug vehicle, achieving better phototherapeutic efficacy and meanwhile alleviating the potential risk of tumor metastasis caused by phototherapy. In this system, besides elongating the photosensitizers' circulation time and enhancing their accumulating efficacy to tumor tissues, LMWH itself also exhibited anti-metastasis efficacy via inhibiting adhesion of platelets to tumor cells and decreasing migration and invasion capability of tumor cells. In vivo efficacy evaluation was conducted on orthotopic 4T1 breast cancer model, and the system of LMWH-ICG-Lip could alleviate metastasis potential of residual tumor cells after irradiation, and elicit optimistic antitumor and anti-metastasis efficacy for phototherapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）