scholarly journals Multicellular tumor spheroids: a relevant 3D model for the in vitro preclinical investigation of polymer nanomedicines

2017 ◽  
Vol 8 (34) ◽  
pp. 4947-4969 ◽  
Author(s):  
Gianpiero Lazzari ◽  
Patrick Couvreur ◽  
Simona Mura
Keyword(s):  
3D Model ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Preclinical Investigation ◽  
P Application

Application of 3D multicellular tumor spheroids to the investigation of polymer nanomedicines.

scholarly journals Single cell organization and cell cycle characterization of DNA stained multicellular tumor spheroids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karl Olofsson ◽  
Valentina Carannante ◽  
Madoka Takai ◽  
Björn Önfelt ◽  
Martin Wiklund
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Drug Distribution ◽  
In Vitro Models ◽  
Biological Information ◽  
Dimensional Structure ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Nuclear Segmentation

AbstractMulticellular tumor spheroids (MCTSs) can serve as in vitro models for solid tumors and have become widely used in basic cancer research and drug screening applications. The major challenges when studying MCTSs by optical microscopy are imaging and analysis due to light scattering within the 3-dimensional structure. Herein, we used an ultrasound-based MCTS culture platform, where A498 renal carcinoma MCTSs were cultured, DAPI stained, optically cleared and imaged, to connect nuclear segmentation to biological information at the single cell level. We show that DNA-content analysis can be used to classify the cell cycle state as a function of position within the MCTSs. We also used nuclear volumetric characterization to show that cells were more densely organized and perpendicularly aligned to the MCTS radius in MCTSs cultured for 96 h compared to 24 h. The method presented herein can in principle be used with any stochiometric DNA staining protocol and nuclear segmentation strategy. Since it is based on a single counter stain a large part of the fluorescence spectrum is free for other probes, allowing measurements that correlate cell cycle state and nuclear organization with e.g., protein expression or drug distribution within MCTSs.

Folic acid-conjugated soybean protein-based nanoparticles mediate efficient antitumor ability in vitro

2016 ◽  
Vol 31 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Weijing Yao ◽  
Qian Zha ◽  
Xu Cheng ◽  
Xin Wang ◽  
Jun Wang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Soy Protein ◽  
Soybean Protein ◽  
Soy Protein Isolate ◽  
Three Dimensional ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Solution Ph ◽  
Protein Nanoparticles

In this study, soy protein isolate was hydrolyzed by compound enzymes to give aqueous soy protein with low molecular weights. Folic acid modified and free soy protein nanoparticles were successfully prepared by a desolvation method as target-specific drug delivery, respectively. Ultraviolet spectrophotometry demonstrated that folic acid was successfully grafted onto soy protein. The shape and size of folic acid modified soy protein nanoparticles were detected by transmission electron microscopy, scanning electron microscope, and dynamic light scattering. In addition, a series of characteristics including kinetic stability, pH stability, and time stability were also performed. Doxorubicin was successfully loaded into folic acid modified soy protein nanoparticles, and the encapsulation and loading efficiencies were 96.7% and 23%, respectively. Doxorubicin-loaded folic acid modified soy protein nanoparticles exhibited faster drug release rate than soy protein nanoparticles in PBS solution (pH = 5). The tumor penetration and antitumor experiments were done using three-dimensional multicellular tumor spheroids as the in vitro model. The results proved that folic acid modified soy protein nanoparticles display higher penetration and accumulation than soy protein nanoparticles, therefore possessing efficient growth inhibitory ability against multicellular tumor spheroids.

Multicellular tumor spheroids as in vitro models for studying tumor responses to anticancer therapies

2020 ◽  
pp. 251-268
Author(s):  
Suchit Khanna ◽  
Ankit Chauhan ◽  
Anant Narayan Bhatt ◽  
Bilikere Srinivasa Rao Dwarakanath
Keyword(s):  
In Vitro Models ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids

scholarly journals Changes in Protein Expression in Two Cholangiocarcinoma Cell Lines Undergoing Formation of Multicellular Tumor Spheroids In Vitro

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118906 ◽  
Author(s):  
Carlo Mischiati ◽  
Blendi Ura ◽  
Leda Roncoroni ◽  
Luca Elli ◽  
Carlo Cervellati ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Lines ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Cholangiocarcinoma Cell

Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems In Vitro

2015 ◽  
Vol 15 (7) ◽  
pp. 4806-4814 ◽  
Author(s):  
Anna M. Privalova ◽  
Svetlana V. Uglanova ◽  
Natalia R. Kuznetsova ◽  
Natalia L. Klyachko ◽  
Yury I. Golovin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids

scholarly journals Encapsulated multicellular tumor spheroids as a novel in vitro model to study small size tumors

2003 ◽  
Vol 57 (12) ◽  
pp. 585-588 ◽  
Author(s):  
Elena Markvicheva ◽  
Lina Bezdetnaya ◽  
Artur Bartkowiak ◽  
Annie Marc ◽  
Jean-Louis Gorgen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Biology ◽  
Cell Encapsulation ◽  
Large Cell ◽  
In Vitro Models ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Vitro Model

Presently multicellular tumor spheroids (MTS) are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be proposed as a novel technique to quickly and easily prepare a large number of spheroids with narrow size distribution within a desirable diameter range. Moreover, the proposed technique for spheroid generation using encapsulated growing tumor cells could provide entirely new avenues to develop a novel spheroid co-culture model (for instance, the in vitro co-cultvation of tumor cells and monocytes, or epithelial cells, or fibroblasts etc). The current research was aimed at developing a simple and reliable method to encapsulate tumor cells and to cultivate them in vitro. In order to generate spheroids, MCF-7 cells were encapsulated and cultivated in 200 ml T-flasks in a 5% CO2 atmosphere at 37?C for 4-5 weeks. The cell proliferation was easily observed using a light microscope. The cells grew in aggregates increasing in size with time. The cell growth resulted in the formation of large cell clusters (spheroids) which filled the whole microcapsule volume in 4-5 weeks.

scholarly journals Confocal Microscopy in Conjunction With Haemocytometry to Evaluate the Imperative Physical Characteristics of Multicellular Tumor Spheroids

2021 ◽  
Author(s):  
Aziz UR RAHMAN
Keyword(s):  
Confocal Microscopy ◽  
Drug Uptake ◽  
Live Cells ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Oriented Growth ◽  
Trypan Blue Exclusion ◽  
Trypan Blue Exclusion Method

Abstract Background: Tumor tissues resist penetration of therapeutic molecules. Multicellular tumor spheroids (MCTSs) were used as an in vitro tumor model. The aim of this study was to determine the growth of MCTSs with the age of spheroids, which could be applied and compared with in vivo drug uptake and penetration. Method: Spheroids were generated by liquid overlay techniques, and their diameter was measured by confocal microscopy for up to two weeks. The trypan blue exclusion method was used to count dead and live cells separately via a hemocytometer. Results: The pentaphysical characteristics of spheroids, including diameter, cell number, volume per cell, viability status, and estimated shell of viable and core of dead cells, were determined. The growth of spheroids was linear over the first week but declined in the 2nd week, which may be due to an overconcentration of dead cells and degraded products inside the spheroids, hence lowering the ratio of live cells in spheroids. Compaction of spheroids occurs from day 3 to day 7, with the mature spheroids having a low amount of extracellular space compared to intracellular volume. Conclusion: Age-oriented growth of MCTSs provides a rationale to predict less rapid penetration as spheroids get older and could be correlated with in vivo tumors to predict pharmaceutical and therapeutic intervention.

scholarly journals Natural and Synthetic Biomaterials for Engineering Multicellular Tumor Spheroids

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2506
Author(s):  
Advika Kamatar ◽  
Gokhan Gunay ◽  
Handan Acar
Keyword(s):  
Cancer Research ◽  
Three Dimensional ◽  
3D Culture ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Natural And Synthetic

The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.

scholarly journals Real-time monitoring of oncolytic VSV properties in a novel in vitro microphysiological system containing 3D multicellular tumor spheroids

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235356
Author(s):  
Kyoung Jin Lee ◽  
Sang Woo Lee ◽  
Ha-Na Woo ◽  
Hae Mi Cho ◽  
Dae Bong Yu ◽  
...  
Keyword(s):  
Real Time ◽  
Multicellular Tumor Spheroids ◽  
Real Time Monitoring ◽  
Tumor Spheroids
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