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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 15 ·11967 · IF 5.6

Recapitulating the Drifting and Fusion of Two-Generation Spheroids on Concave Agarose Microwells

Rong Pan,Xiaoyan Yang,Ke Ning,Yuanyuan Xie,Feng Chen,Ling Yu

Cells with various structures and proteins naturally come together to cooperate in vivo. This study used cell spheroids cultured in agarose micro-wells as a 3D model to study the movement of cells or spheroids toward other spheroids. The formation dynamics of tumor spheroids and the interactions of two batches of cells in the agarose micro-wells were studied. The results showed that a concave bottom micro-well (diameter: 2 mm, depth: 2 mm) prepared from 3% agarose could be used to study the interaction of two batches of cells. The initial tumor cell numbers from 5 × 103cells/well to 6 × 104cells/well all could form 3D spheroids after 3 days of incubation. Adding the second batch of DU 145 cells to the existing DU 145 spheroid resulted in the formation of satellite cell spheroids around the existing parental tumor spheroid. Complete fusion of two generation cell spheroids was observed when the parental spheroids were formed from 1 × 104and 2 × 104cells, and the second batch of cells was 5 × 103per well. A higher amount of the second batch of cells (1 × 104cell/well) led to the formation of independent satellite spheroids after 48 h of co-culture, suggesting the behavior of the second batch of cells towards existing parental spheroids depended on various factors, such as the volume of the parental spheroids and the number of the second batch cells. The interactions between the tumor spheroids and Human Umbilical Vein Endothelial Cells (HUVECs) were modeled on concave agarose micro-wells. The HUVECs (3 × 103cell/well) were observed to gather around the parental tumor spheroids formed from 1 × 104, 2 × 104, and 3 × 104cells per well rather than aggregate on their own to form HUVEC spheroids. This study highlights the importance of analyzing the biological properties of cells before designing experimental procedures for the sequential fusion of cell spheroids. The study further emphasizes the significant roles that cell density and the volume of the spheroids play in determining the location and movement of cells.Keywords:cell spheroids;bio-assembling;spheroid fusion;3D cell culture;agarose array

CAS / MDL: 9012-36-6
研究领域: 癌症生物学 · 细胞生物学 · 组织工程
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JOURNAL OF CHROMATOGRAPHY A · 2023 · IF 4.1

Core-shell metal-organic framework/silica hybrid with tunable shell structure as stationary phase for high performance liquid chromatography

Jiafei Wang,Yuqing He,Xiang Wan,Fazhi Xie,Yuanshe Sun,Tong Li,Qin Xu,Donglin Zhao,Qishu Qu

Metal-organic framework/silica composite (SSU) were prepared by growing UiO-66 on the amino-functionalized SiO 2 core-shell spheres (SiO 2 @ d SiO 2 ) via a simple one-pot synthesis approach. By controlling the concentration of Zr 4+ , the obtained SSU have two different morphologies: spheres-on-sphere and layer-on-sphere. The spheres-on-sphere structure is formed by the aggregation of UiO-66 nanocrystals on the surface of SiO 2 @ d SiO 2 spheres. SSU-5 and SSU-20, which contain spheres-on-sphere composites have mesopores with a pore size of about 45 nm in addition to the characteristic micropores of UiO-66 with a pore size of 1 nm. In addition, UiO-66 nanocrystals were grown both inside and outside the pores of SiO 2 @ d SiO 2 , resulting in a 27% loading of UiO-66 in the SSU. The layer-on-sphere is the surface of SiO 2 @ d SiO 2 covered with a layer of UiO-66 nanocrystals. SSU with this structure has only a characteristic pore size of about 1 nm belonging to UiO-66 and is therefore not suitable as a packed stationary phase for high performance liquid chromatography. The SSU spheres were packed into columns and tested for the separation of xylene isomers, aromatics, biomolecules, acidic and basic analytes. With both micropores and mesopores, SSU with spheres-on-sphere structure achieved baseline separation of both small and large molecules. Efficiencies up to 48,150, 50,452 and 41,318 plates m   −   1 were achieved for m -xylene, p -xylene and o -xylene, respectively. The relative standard deviations of the retention times of anilines for run-to-run, day-to-day and column-to-column were all less than 6.1%. The results show that the SSU with spheres-on-sphere structure has great potential for high performance chromatographic separation.

研究领域: 分析化学 · 材料科学 · 色谱学
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Nanomaterials · 2019 ·Vol. 9 ·期 2 ·132 · IF 4.034

Synthesis of ZnxCd1-xSe@ZnO Hollow Spheres in Different Sizes for Quantum Dots Sensitized Solar Cells Application

Libo Yu,Zhen Li

ZnxCd1-xSe@ZnO hollow spheres (HS) were successfully fabricated for application in quantum dot sensitized solar cells (QDSSCs) based on ZnO HS through the ion-exchange process. The sizes of the ZnxCd1-xSe@ZnO HS could be tuned from ~300 nm to ~800 nm using ZnO HS pre-synthesized by different sizes of carbonaceous spheres as templates. The photovoltaic performance of QDSSCs, especially the short-circuit current density (Jsc), experienced an obvious change when different sizes of ZnxCd1-xSe@ZnO HS are employed. The ZnxCd1-xSe@ZnO HS with an average size distribution of ~500 nm presented a better performance than the QDSSCs based on other sizes of ZnxCd1-xSe@ZnO HS. When using the mixture of ZnxCd1-xSe@ZnO HS with different sizes, the power conversion efficiency can be further improved. The size effect of the hollow spheres, light scattering, and composition gradient structure ZnxCd1-xSe@ZnO HS are responsible for the enhancement of the photovoltaic performance.Keywords:alloyed quantum dots;hollow spheres;sensitized solar cells;zinc oxide

研究领域: 材料科学 · 能源科学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2019 · IF 3.375

Patterned PHEMA Films Synthesized by Redox Polymerization for Multicellular Spheroid Generation

Yifan Yun,Ying Guan,Yongjun Zhang

Patterned hydrogel films are attractive for the generation of 3D multicellular spheroids, a new in vitro cell model. Traditional methods for their synthesis, such as photolithography and micromolding, usually require a template and are difficult to fit into commercial cell culture plates. Here a simple method to synthesize patterned poly(2-hydroxyethyl methacrylate) (PHEMA) films were developed. First PHEMA films were synthesized in situ in the wells of cell culture plates by bulk redox polymerization of the monomer. Films with a corrugated surface were usually obtained. Fortunately a narrow range of initiator concentration was identified in which smooth films could be obtained. Then water was added to swell the films and wrinkling patterns were produced spontaneously. The shape and size of the patterns can be controlled by adjusting cross-link density and film thickness. Under optimized conditions, films with regular hexagonal patterns were obtained successfully. The patterned PHEMA films were further used to generate multicellular spheroids. The resulting spheroids exhibit high viability and narrow size distribution.

CAS / MDL: 94-36-0 100-10-7 97-90-5
研究领域: 生物材料学 · 细胞生物学 · 组织工程
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MACROMOLECULAR BIOSCIENCE · 2022 ·Vol. 22 ·期 4 ·2100498 · IF 5.859

Self-Organization Formation of Multicellular Spheroids Mediated by Mechanically Tunable Hydrogel Platform: Toward Revealing the Synergy of Chemo- and Noninvasive Photothermal Therapy against Colon Microtumor

Yi Zhang,Zhao-bin Guo,Yu-min Nie,Guan-ping Feng,Man-jiao Deng,Yi-min Hu,Hui-jie Zhang,Yin-yi Zhao,Yi-wei Feng,Ting-ting Yu,Ke Hu

Three-dimensional (3D) tumor cell culture offers a more tissue-recapitulating model in cancer treatment evaluation. However, conventional models based on cell-substrate adhesion deprivation are still of insufficient real tumor mimic. In this work, a novel method is proposed for inducing multicellular spheroids (MCSs) formation based on hydrogel with tunable microenvironmental properties. Colon tumor cells DLD1 cultured on hydrogel substrate with proper physical stimulation form MCSs via self-organization. Chemotherapy based on clinical drug and far-infrared photothermal therapy is evaluated with DLD1 MCSs obtained by this method. The synergism of chemotherapy and noninvasive photothermal therapy based on graphene device is further verified in MCSs model and it is believed this method holds potential in in vitro anti-tumor strategies evaluation for precision medicine.

研究领域: 肿瘤学 · 生物材料学 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Enhanced transdermal drug delivery and breast cancer spheroid penetration using hyaluronic acid-coated ethosomes

Muhammad Umer Rajput,Syed Wajahat Ali,Wajiha Kainat,Sahar Madani,Weiping Ding

Transdermal drug delivery systems offer a non-invasive route for administering medications, providing a controlled and sustained release of therapeutic agents through the skin. Here, the hyaluronic acid modified ethosomes loaded with paclitaxel (HA-ES-PTX) and ethosomes loaded with PTX (ES-PTX) nanoparticles were synthesized for treating cancer via skin. The ES-PTX were successfully prepared by the thin film hydration method, and then HA-ES-PTX were coated through electrostatic attraction, which caused the attraction of hyaluronic acid (HA) on the surface of cationic ethosomes. Morphological studies by TEM, particle size/zeta potential by DLS, and encapsulation efficiency by a nanodrop spectrophotometer were conducted. Cell uptake studies showed that hyaluronic acid-modified ethosomes loaded with calcein (HA-ES-Calcein) were more internalized than non-modified ethosomes (ES-calcein) and free calcein. MTT assay on breast cancer 4T1 and MDA-MB-231 cell lines revealed that HA-ES-PTX was more cytotoxic than ES-PTX and free PTX. In vitro, Franz diffusion cell experiments with rat skin indicated HA-ES-PTX had increased penetration compared to ES-PTX and hydroethanolic PTX. Finally, 3D breast tumor spheroids were constructed using MCF-7 and HFL1 cell lines. ES-PTX and HA-ES-PTX were introduced into the spheroids, and their sizes were visualized over five days. The results indicated that HA-ES-PTX offers a safe and efficient transdermal drug delivery system and provides significant anti-tumor effects on the 3D breast tumor spheroid.

CAS / MDL: 33069-62-4
研究领域: 药剂学 · 肿瘤学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SUPRAMOLECULAR CHEMISTRY · 2018 · IF 1.451

Microsphere-to-nanotube transition via in situ sonication triggered in a supramolecular self-assembly system based on triphenylamine derivative

Xinhua Cao,Aiping Gao,Dan Liu,Na Zhao,Qianqian Ding,Yiran Li

A new gelator 1 containing triphenylamine was designed and synthesized, and formed stable gel in ethyl acetate. The self-assembly process of molecule 1 was thoroughly investigated. The solid microsphere structure formed in gel 1 could be turned into nanotube in the transition process of gel to gel via sonication. At the same time, the intermolecular hydrogen bond of self-assembly system was obviously enhanced under sonication. The XRD and water contact angle experiments results of xerogel 1 before and after sonication showed great difference. The hydrophobicity of xerogel 1 film was obviously decreased with the change of contact angle from 142° to 129° after sonication at 100 W for one minute. From the results, it was possible that the solid microsphere was re-dissolved and further reassembled into nanotube. To our knowledge, it was the first example that the solid sphere structure was changed into nanotube in self-assembly system via sonication.

研究领域: 材料科学 · 化学
✓ 已验证 DOI 高影响因子
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Biomaterials Science · 2014 ·Vol. 3 ·期 3 ·500-508 · IF 0

Hydrogen-bonding dramatically modulates the gene transfection efficacy of surface-engineered dendrimers

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.

CAS / MDL: 3397-62-4
研究领域: 生物化学 · 基因治疗 · 材料科学
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CARBON · 2022 · IF 11.307

A general confinement co-assembly strategy enabling cross-dimensional supraspheres for boosting electrochemical performance

Dandan Han,Qian Zhou,Yan Xia,Dongting Huang,Jieqiong Qin,Lixia Wang,Xiaopeng Wang,Xianfu Zheng,Dan Wu

The bottom-up assembly utilizing nanocrystals (NCs) as building blocks is a highly anticipated approach to access novel metamaterials. Limited by the library of binary spherical assembly, colloidal components of building blocks are necessarily extended for targeting the desired assembled-superstructure with emergent properties. Here, a generalized approach is presented that carbon nanotubes (CNTs) capped with long-chain hydrocarbon ligands, as creative colloidal components, can be compatibly co-assembled with various NCs into binary supraspheres based on a confinement microemulsion environment. Such cross-dimensional assemblies possess the structural merits of excellent conductivity, abundant voids and high stability, thus synergistically boosting its electrochemical performance. As a proof of concept , the co-assembled CoFe 2 O 4 /CNTs supraspheres exhibit extraordinary capacity (890 mAh g −1 at 0.5 A g −1 ), rate capability (318 mAh g −1 at 20 A g −1 ), and structural stability (458 mAh g −1 at 5 A g −1 after 1000 cycles) relative to pure CoFe 2 O 4 when evaluated in Li-ion battery. Beyond that, its derived phosphides CoFeP/CNTs assemblies outperform most of the state-of-art electrodes when acting as electrocatalysts for hydrogen evolution reactions (HER). This work provides a new perspective for constructing superstructures of NCs for potential applications in energy storage devices.

研究领域: 材料科学 · 能源存储 · 纳米技术
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Superhydrophobic and Photocatalytic Synergistic Self-Cleaning Coating Constructed by Hierarchically Structured Flower-like Hollow SiO2@TiO2 Spheres with Oxygen Vacancies

Ruyue Guo,Yan Bao,Xi Zheng,Jie Chen,Hong Yang,Wenbo Zhang,Chao Liu,Jiachen Xu

The self-cleaning coating has both superhydrophobic physical and photocatalytic chemical self-cleaning properties, which has attracted the wide attention of researchers in recent years. First, the flower-like hollow SiO2@TiO2 spheres with oxygen vacancies (rFHSTs) were prepared by the liquid-phase reduction method, in which several different functional components were integrated. Meanwhile, the influence mechanisms of the physical structure and chemical composition on the photocatalytic properties are discussed in detail. The results proved that rFHSTs exhibited the enhanced photoresponse range and photocatalytic degradation performance in visible light because of the synergistic effect of the microstructure (internal cavity, 3D flower-like nanosheet), SiO2/TiO2 heterojunction structure, and oxygen vacancies. After that, superhydrophobic modified rFHSTs were used as fillers to fabricate PVA/PFDTS-rFHSTs composite coatings with both physical and chemical self-cleaning properties. The self-cleaning performances and principles of the composite coating were examined and explored. The results showed that the low surface energy of the hydrophobic chain segment, the inherent particle effect, and the photocatalytic activity of rFHSTs were responsible for the superhydrophobic and photocatalytic effects, finally endowing the composite coating with self-cleaning performance. In short, this study is profound for the development and application of self-cleaning coatings with both physical and chemical performances.

CAS / MDL: 9002-89-5 15681-89-7
研究领域: 材料科学 · 表面化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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eLife · 2025 · IF 0

Non-destructive in situ monitoring of structural changes of 3D tumor spheroids during the formation, migration, and fusion process

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.

CAS / MDL: 9012-36-6
研究领域: 细胞生物学 · 肿瘤学 · 显微成像技术
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Biotechnology Journal · 2024 ·Vol. 19 ·期 2 ·2300427 · IF 3.2

High throughput generating stable spheroids with tip-refill wafer

Xiaoyan Yang,Rong Pan,Ke Ning,Yuanyuan Xie,Feng Chen,Wei Sun,Ling Yu

Three-dimensional (3D) cell cultures have garnered significant attention in biomedical research due to their ability to mimic the in vivo cellular environment more accurately. The formation of 3D cell spheroids using hanging drops has emerged as a cost-effective and crucial method for generating uniformly-sized spheroids. This study aimed to validate the potential of a tip-refill wafer (TrW), a disposable laboratory item used to hold pipette tips, in facilitating 3D cell culture. The TrW allows for easy generation of hanging drops by pipetting the solution into the holes of the wafer. The mechanical stability of the hanging drops is ensured by the surface wettability and thickness of the TrW. Hanging drops containing 60-µL of solution remained securely attached to the TrW even when subjected to orbital shaking at 210 rpm. The exceptional resistance to mechanical shaking enabled the use of inertial focusing to facilitate spheroid formation. This was demonstrated through live/dead cell staining, quantitative polymerase chain reaction (qPCR) analysis, and cytoskeleton staining, which revealed that horizontal orbiting at 60 rpm for 15 min promoted cell aggregation and ultimately led to the formation of 3D spheroids. The spheroid harvest rate is 96.1% ± 3.5% across three TrWs, each containing 60 hanging drops. In addition to generating mono-culture 3D spheroids, the TrW-based hanging drop platform also enables the formation of multicellular spheroids, and on-demand pairing and fusion of spheroids. The TrW is a disposable item that does not require any fabrication or surface modification procedures, further enhancing its application potential in conventional biological laboratories.

研究领域: 生物医学工程 · 细胞生物学 · 分子生物学
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