Biomaterials Science
·
2014
·Vol. 3
·期 3
·500-508
·
IF 0
Naimin Shao,Hui Wang,Bingwei He,Yu Wang,Jianru Xiao,Yitong Wang,Qiang Zhang,Yujia Li,Yiyun Cheng
Dendrimers have shown great promise in the design of efficient gene vectors. However, high transfection efficacy is usually associated with serious cytotoxicity for these cationic polymers. Here, we report a facile strategy to prepare surface-engineered dendrimers with a dramatic transfection efficacy and reduced cytotoxicity. Surface-engineered dendrimers with multiple hydrogen bonding ligands such as guanamine and nucleobase derivatives show superior efficacy and low cytotoxicity on commonly used cells as well as 3D tumor spheroids to representative transfection reagents such as Lipofectamine 2000. Complementary multiple hydrogen bonding interactions between the modified ligands and DNA nucleobases play essential roles in efficient gene transfection. The hydrogen-bond modulation strategy represents a promising tool in the design of highly efficient and less cytotoxic gene materials.
研究领域:
生物化学
·
基因治疗
·
材料科学
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DOI
PubMed
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Ximeng Wang,Zhengya Yue,Wencheng Zhong,Lin Wang,Li Shang
Gold nanoclusters (AuNCs) have garnered significant attention in biomedical applications, particularly in biosensing, cancer therapy, and imaging, due to their unique optical property, good biocompatibility, and distinct bioactivity. Understanding the cellular uptake behavior of AuNCs is critical to improve the efficacy of their applications, whose mechanism has not been adequately validated. In this work, we synthesized AuNCs with varying surface modifications to quantify the exact law of surface charge on the cellular uptake of AuNCs in a multidimensional manner by using 3D multicellular tumor spheroids of both HeLa cells and MCF-7 cells as the model system. By the combined use of fluorescence live cell imaging and inductively coupled plasma–mass spectrometry, we systematically investigated the effect of surface charge on their uptake rate, intracellular versus intercellular distribution, and penetration depth in a quantitative manner. Our results showed that the cellular uptake of AuNCs was strongly charge dependent, with uptake efficiency increasing with the degree of surface positive charges. A similar charge-dependent uptake behavior was observed in both 2D cell cultures and 3D multicellular tumor spheroids, but the difference in 3D spheroids was less pronounced, in comparison to the 2D model. The effect of AuNCs’ surface charge on the cellular uptake has been quantified in multiple dimensions in this work, which also provides crucial knowledge for effective cancer therapeutics and imaging applications based on AuNCs and other nanomaterials.
研究领域:
生物医学工程
·
分子生物学
·
纳米医学
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DOI
PubMed
高影响因子
eLife
·
2025
·
IF 0
Ke Ning,Yuanyuan Xie,Wen Sun,Lingke Feng,Can Fang,Rong Pan,Yan Li,Ling Yu
For traditional laboratory microscopy observation, the multi-dimensional, real-time, in situ observation of three-dimensional (3D) tumor spheroids has always been the pain point in cell spheroid observation. In this study, we designed a side-view observation petri dish/device that reflects light, enabling in situ observation of the 3D morphology of cell spheroids using conventional inverted laboratory microscopes. We used a 3D-printed handle and frame to support a first-surface mirror, positioning the device within a cell culture petri dish to image cell spheroid samples. The imaging conditions, such as the distance between the mirror and the 3D spheroids, the light source, and the impact of the culture medium, were systematically studied to validate the in situ side-view observation. The results proved that placing the surface mirror adjacent to the spheroids enables non-destructive in situ real-time tracking of tumor spheroid formation, migration, and fusion dynamics. The correlation between spheroid thickness and dark core appearance under light microscopy and the therapeutic effects of chemotherapy doxorubicin and natural killer cells on spheroids’ 3D structure was investigated.
研究领域:
细胞生物学
·
肿瘤学
·
显微成像技术
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DOI
PubMed
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Zhiwei Hu,Yuanxiong Cao,Edgar A. Galan,Liang Hao,Haoran Zhao,Jiyuan Tang,Gan Sang,Hanqi Wang,Bing Xu,Shaohua Ma
Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that have demonstrated great potential in drug evaluation for personalized medicine. Here, we used a perfusable vascularized tumor spheroid-on-a-chip to simulate the tumor microenvironment in vivo and demonstrated that the PHD inhibitor dimethylallyl glycine prevents the degradation of normal blood vessels while enhancing the efficacy of the anticancer drugs paclitaxel and cisplatin in human esophageal carcinoma (Eca-109) spheroids. Our results point to the potential of this model to evaluate anticancer drugs under more physiologically relevant conditions.
研究领域:
肿瘤学
·
药理学
·
生物工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xiangxiang Zhang,Chao Li,Shubin Li,Xuefeng Tang,Jingjing Zhao,Weili Xu,Xiaojun Han
Three-dimensional (3D) tumor spheroids in vitro have great potential in drug discovery and tissue engineering due to their similarity to real tissues. Herein, we develop a simple strategy, with time and cost-effective, noninvasive characters to produce high-throughput 3D tissue spheroids using the magneto-Archimedes effect. This method is versatile in producing various morphologies of tumor spheroids by using different templates, as well as spatially coded tumor spheroids by adding different cells in the defined orders. The prepared tumor spheroids are similar to the mouse homograft tumors, as confirmed by immunofluorescence experimental results. We demonstrate that the prepared tumor spheroids can be used for anticancer drug screening, tumor inoculations, and the study of chemical signal transduction between artificial cell aggregates and tumor tissues. Temozolomide (TMZ) is found to be more effective than 5-FU toward gliomas. Further, C6 tumor spheroids are successfully inoculated into mice to grow tumors with a rapid growth rate than free cells. In the hybrid structure containing artificial cell aggregates and tumor spheroids, reactive oxygen species (H2O2) are generated in the artificial cell aggregates, which diffuse into tumor spheroids to cause the redistribution of intracellular Ca2+ in tumor cells, consequently inducing cell apoptosis. This method is easy to scale up by using large magnets. It provides great potential in complicated tissue structure construction, antitumor drug screening, and tissue engineering.
研究领域:
生物医学工程
·
肿瘤学
·
药物开发
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Mingxia Lu,Yuying Shen,Jiayu Zheng,Sen Wang,Mingliang Fan,Hongxu Lu
Glycopolymeric nanoparticles are widely employed in biomedical applications due to their high targeting ability, biocompatibility, and biodegradability. The pendant saccharides serve as targeting ligands to be explicitly coordinated to receptors on cell membrane surfaces. However, proteins in the blood often absorb onto the nanoparticle surface, potentially impacting the exposure and effectiveness of the saccharide ligands for targeted delivery. To elucidate the protein absorption effects, we prepared micelles decorated with different percentages of fructose moieties and evaluated the bioactivity of nanoparticles using 2D cell culture, tumor spheroid, liver organoid, and coculture models. The 2D cell culture model did not show a significant difference in activity between protein-coated and non-coated micelles. However, a dramatic decrease in cellular uptake and penetration ability of micelles was observed in 3D tumor spheroids after protein absorption. Additionally, protein absorption notably increased micelle uptake in liver organoids. In the coculture model, protein absorption reduced micelle uptake in tumor spheroids while favoring uptake in liver organoids. Our work suggests that decreasing non-specific protein absorption of glycopolymeric nanoparticles could enhance their delivery efficiency. These findings underscore the importance of understanding protein interactions in nanoparticle applications for drug delivery.
研究领域:
生物医学工程
·
药物递送系统
·
细胞生物学
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产品关联
DOI
高影响因子
LAB ON A CHIP
·
2013
·Vol. 14
·期 3
·471-481
·
IF 5.697
Xiaokang Li,Xinyong Zhang,Shan Zhao,Jingyu Wang,Gang Liu,Yanan Du
Cell-based high throughput drug screening accelerates the pace of drug discovery which is routinely operated on planar high-density multi-well plates with sophisticated robotic liquid-dispensing systems for cell seeding and drug administration. Considerable efforts have been made to upgrade in vitro cellular models from 2D to a more biomimetic 3D configuration. For instance, in anti-cancer drug screening, tumor spheroids are increasingly applied as a gold-standard 3D model exhibiting cellular behaviors and drug responses distinguishable from the 2D counterpart. However, translation of spheroids to high throughput drug screening is challenging since pre-formation of spheroids and subsequent translocation to multi-well plates for drug testing are usually uncontrollable and time/reagent consuming and cell loss is inevitable during medium exchange for drug testing. Here we present an off-the-shelf micro-scaffold array chip which enables high throughput 3D cell culture, drug administration and quantitative in situ assays entirely on the same chip. The sponge-like micro-scaffolds functioned both as absorbents to realize parallel auto-loading of cells or drugs and as barriers to prevent cell loss during medium exchange via centrifugation. Rapid manual loading of cell suspensions or drugs into the 96 isolated micro-scaffolds on the chip was achieved in the timescale of several seconds, meanwhile with total medium consumption reduced to the order of microliters. Proof of concept demonstration of drug cytotoxicity testing was performed on multiple cancer cells using common benchtop equipment, making it accessible to most biomedical labs with basic cell culture setups. Higher cellular drug resistance was constantly obtained with this platform compared to the planar cultures, which was partially attributed to the malignant phenotype of cancer cells yielded by enhanced cell–matrix interactions in the micro-scaffolds. Interestingly, the high drug resistance of 3D cultured cells in the micro-scaffold was shown to be density-independent in contrast to the density-dependent drug response for 2D cultured cells, indicating intrinsic differences between the two culture models. This platform is expected to facilitate upgrade of the current cell-based high throughput drug testing to the 3D level and be widely applicable across various disciplines.
研究领域:
生物医学工程
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2022
·
IF 8.101
Jin Li,Zi-Hui Wang,Ya-Min Dang,Dan-Ni Li,Zhen Liu,Da-Peng Dai,Jian-Ping Cai
MTH1 protein can sanitize the damaged (d)NTP pool and MTH1 inhibitors have been developed to impede the growth of rapidly proliferating tumor cells; however, the effect of MTH1 inhibition on breast cancer stemness has not been reported yet. Here, we constructed breast cancer cell lines with the stable depletion of MTH1. MTH1 suppression clearly increased the ratio of CD44 + CD24 −/low subpopulations and promoted the formation of tumorspheres in MCF7 and T47D cells. RNA expression profiling, RT–qPCR and Western blotting showed the upregulation of master stem cell transcription factors Sox2 , Oct4 and Nanog in MTH1 knockdown cells. GSEA suggested and Western blotting verified that MTH1 knockdown increased the expression of phosphorylated STAT3 (Tyr705). Furthermore, we indirectly demonstrated that the increased concentration of 8-oxo-dGTP and 8-oxo-GTP in MTH1 -knockdown cells and exogenous 8-oxoGTP, rather than 8-oxo-dGTP, could significantly increase the phosphorylation of STAT3. In conclusion, this work indicates that MTH1 inhibition increased the proportion of breast cancer stem cells (BCSCs) and promoted stemness properties in MCF7 cells.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2023
·
IF 6.1
Chenyi Gao,Kunpeng Jia,Jun Fang,Xuan Zhu,Jianming Hu,Yi Zhang,Jinxin Jiang,Xiuyan Yu,Danting Wang,Haochen Gu,Zhigang Chen
Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in many human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1 ). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2024
·Vol. 14
·期 9
·482
·
IF 3.4
Zihan Zhu,Yaqi Zhang,Lei Wang,Haoyuan Geng,Min Li,Shiping Chen,Xiao Wang,Panpan Chen,Chenglong Sun,Chao Zhang
Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.
研究领域:
肿瘤学
·
代谢组学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Haoyuan Geng,Panpan Chen,Yaqi Zhang,Zihan Zhu,Yanfang Zhao,Xiao Wang,Chenglong Sun
Ferroptosis, as an iron-dependent cell death mediated by lipid peroxidation, has sparked great interest in the tumor research community. Targeting ferroptosis has been proven to be a new therapeutic opportunity for inhibiting tumor growth. However, it is challenging to precisely characterize the metabolic pattern of ferroptosis in heterogeneous tumors and further identify ferroptosis-associated metabolic vulnerabilities for tumor treatment. In this work, we developed a spatiotemporally resolved method to image ferroptosis-associated metabolic alterations in 3D tumor spheroids by combining mass spectrometry imaging and stable isotope tracing techniques. The construction of a 3D tumor spheroid model allows for a more accurate simulation of ferroptosis, and the introduction of MALDI-MSI enables in situ screening of abnormal molecules in tumor tissues. Using this method, we showed that the expression proportion of nC═C = 4 polyunsaturated fatty acids, including arachidonic acid (FA-20:4) and adrenic acid (FA-22:4), were upregulated in RSL3-induced 3D tumor ferroptosis models. And the isotope tracing experiment revealed that the absorption of fatty acids and the biosynthesis of polyunsaturated fatty acids were significantly increased during ferroptosis. In addition, we discovered that arachidonic acid and adrenic acid supplementation render tumor cell sensitive to ferroptosis, thereby limiting the growth of tumor cells and the formation of 3D tumor spheroids. Such findings provide significant clues for understanding the metabolic signatures of tumor ferroptosis and raise the possibility to screen potential metabolic vulnerabilities for better tumor treatment in combination with ferroptosis.
研究领域:
癌症生物学
·
代谢组学
·
治疗开发
·
分析化学
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产品关联
DOI
PubMed
高影响因子
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
·
2025
·Vol. 72
·期 11
·3233-3243
·
IF 4.5
Kun Qian,Chenguo Yao,Yancheng Wang,Qiang Yang,Sizhe Xiang,Qiying Pei,Ting Zhu,Hongmei Liu,Shoulong Dong
Two major reasons why chemotherapy and immunotherapy have limited efficacy in treating gliomas are the blood-brain barrier and the dense, solid structure of the glioma. Pulsed electric fields have been a powerful tool for ablating solid tumors, and narrowing pulse duration can improve the field homogeneity penetrating into the tumor. In this study, we used multicellular tumor spheroids (MCTSs) as a model to explore the potential of ultrashort nanosecond pulses to inhibit tumor cell activity while disrupting their dense drug-resistant barriers. Exposure to ultrashort pulsed electric fields can significantly inhibit the viability of U-87 MG, C6, and GL261 spheroids, as indicated by reduced intracellular ATP content. Meanwhile, the proliferative abilities of tumor cells were suppressed, as evidenced by reduced Ki67 protein expression. In addition, it is notable that, after exposure to electric fields, the volume of spheroids increased dramatically. We hypothesize that ultrashort pulsed electric fields can reduce tumor compactness, thereby facilitating drug delivery for immunotherapy and chemotherapy. Immunofluorescence results showed that the cell-cell junction was broken by ultrashort pulsed electric fields with lower expression of adherens junction protein N-cadherin and tight junction protein ZO-1. It is evidenced that the capability of ultrashort pulsed electric fields to downregulate the intercellular adherence, as well as suppress the epithelial-mesenchymal transition, a key process of metastasis of cancer cells. At last, aqueous fluorescent nanoparticles were applied to simulate the anticancer drug or therapeutic antibodies. Under the supervision of fluorescence microscopy, the degree of nanoparticles penetrating into the spheroids was positively related to the number of ultrashort pulsed electric fields, marked with a higher fluorescent signal from the inner quiescent zone or a necrotic core. In conclusion, we emphasize that ultrashort pulsed electric fields could be promising for downgrading the compactness of glioma tumors, being a powerful assisted therapy for the delivery of anticancer drugs and therapeutic antibodies.
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PubMed
高影响因子
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