scholarly journals CEA-targeted nanoparticles allow specific in vivo fluorescent imaging of colorectal cancer models

Nanomedicine ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. 1223-1231 ◽  
Author(s):  
James P Tiernan ◽  
Nicola Ingram ◽  
Gemma Marston ◽  
Sarah L Perry ◽  
Jo V Rushworth ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluorescent Imaging ◽  
Targeted Nanoparticles ◽  
Cancer Models

scholarly journals O23: CHARACTERISING PATIENT-DERIVED COLORECTAL CANCER TISSUE-ORIGINATED ORGANOIDAL SPHEROIDS FOR HIGH-THROUGHPUT MICROFLUIDIC APPLICATIONS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluid Flow ◽  
High Throughput ◽  
Microfluidic Devices ◽  
In Vitro Models ◽  
Fluorescent Imaging ◽  
Cancer Tissue ◽  
Cell Models

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.

scholarly journals In vivo biodistribution and passive accumulation of upconversion nanoparticles in colorectal cancer models via intraperitoneal injection

RSC Advances ◽  
2017 ◽  
Vol 7 (50) ◽  
pp. 31588-31596 ◽  
Author(s):  
Yilin Gao ◽  
Xingjun Zhu ◽  
Yuwen Zhang ◽  
Xiaofeng Chen ◽  
Li Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Injection ◽  
Upconversion Nanoparticles ◽  
Tumour Targeting ◽  
Biological Processes ◽  
In Vivo Biodistribution ◽  
Cancer Models ◽  
Targeting Effectiveness

Cit-UCNPs after IP injection exhibited significantly different biological processes from those after IV injection. The passive-tumour targeting effectiveness of cit-UCNPs via the IP route was higher than that via the IV route.

scholarly journals Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Yun Zhou ◽  
Ke Li ◽  
Fan Li ◽  
Shuang Han ◽  
Yang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Chemotherapy ◽  
Targeted Delivery ◽  
Fluorescent Imaging ◽  
Targeted Nanoparticles ◽  
Continuous Release ◽  
Tumor Tissues ◽  
Dual Drug

For the patients with hepatocellular carcinoma (HCC), conventional chemotherapy is insufficient or has no benefit. Although combination chemotherapy has been proven as an efficient strategy to enhance anti-HCC efficacy, some barriers, such as low bioavailability and side effects, are limiting clinical development. In order to overcome disadvantages of combination chemotherapy in HCC, targeted nanoparticles (NPs) simultaneously loaded with doxorubicin (DOX) and ABT-199 in an optimal synergistic ratio were developed. First, the most synergistic combination with DOX was screened from ABT-199, ABT-263, and ABT-737. Among them, ABT-199 showed optimal synergy with DOX in a ratio of 10 : 1. Then, cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were used in coencapsulations of those two drugs. Dual-drug synergistic nanoparticles (DDS NPs) were constructed by absorption of DOX NPs around ABT-199 micelles with an optimal ratio via electrostatic interaction. The shape of DDS NPs was similar to a raspberry, and the size was 112.6±13.4 nm. The encapsulation efficiencies of DOX and ABT-199 in DDS NPs were 90.2±4.3% and 94.7±2.8%, respectively; meanwhile, the drug loadings were 1.5±0.4% and 14.1±1.1%, respectively. After 72 h of dialysis, 95% of ABT-199 remained and less than 50% of DOX was released. In vitro investigation showed that the drugs in DDS NPs maintained the treated effect in three HCC cell lines; moreover, DDS NPs could perform intracellular delivery of dual drugs and exhibited continuous release of the drugs into different targets. Low in vivo toxicity was found after the acute toxicity test. In vivo fluorescent imaging revealed that DDS NPs could efficiently target and accumulate in the tumor tissues and be maintained more than 72 h after intravenous injection. Compared with free drugs, DDS NPs with the same dosages exhibited a more significant antitumor effect in the HCC xenograft mouse model. The results indicated that DDS NPs have great potential in HCC chemotherapy.

scholarly journals A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 227
Author(s):  
Eileen Reidy ◽  
Niamh A. Leonard ◽  
Oliver Treacy ◽  
Aideen E. Ryan
Keyword(s):  
Colorectal Cancer ◽  
3D Model ◽  
Treatment Options ◽  
3D Models ◽  
In Vivo Studies ◽  
The Past ◽  
Monolayer Cultures ◽  
Cancer Models

Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.

scholarly journals Antibody PEGylation in bioorthogonal pretargeting with trans-cyclooctene/tetrazine cycloaddition: in vitro and in vivo evaluation in colorectal cancer models

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Aurélie Rondon ◽  
Nancy Ty ◽  
Jean-Baptiste Bequignat ◽  
Mercedes Quintana ◽  
Arnaud Briat ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
In Vivo Evaluation ◽  
Cancer Models

scholarly journals Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models

Oncotarget ◽  
2016 ◽  
Vol 7 (26) ◽  
pp. 39595-39608 ◽  
Author(s):  
Michael S. Lee ◽  
Timothy L. Helms ◽  
Ningping Feng ◽  
Jason Gay ◽  
Qing Edward Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Models

Fluorescent proteins for in vivo imaging, where's the biliverdin?

2020 ◽  
Vol 48 (6) ◽  
pp. 2657-2667
Author(s):  
Felipe Montecinos-Franjola ◽  
John Y. Lin ◽  
Erik A. Rodriguez
Keyword(s):  
Hydrogen Peroxide ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Fluorescent Imaging ◽  
Infrared Light ◽  
Red Fluorescent Protein ◽  
Color Palette

Noninvasive fluorescent imaging requires far-red and near-infrared fluorescent proteins for deeper imaging. Near-infrared light penetrates biological tissue with blood vessels due to low absorbance, scattering, and reflection of light and has a greater signal-to-noise due to less autofluorescence. Far-red and near-infrared fluorescent proteins absorb light >600 nm to expand the color palette for imaging multiple biosensors and noninvasive in vivo imaging. The ideal fluorescent proteins are bright, photobleach minimally, express well in the desired cells, do not oligomerize, and generate or incorporate exogenous fluorophores efficiently. Coral-derived red fluorescent proteins require oxygen for fluorophore formation and release two hydrogen peroxide molecules. New fluorescent proteins based on phytochrome and phycobiliproteins use biliverdin IXα as fluorophores, do not require oxygen for maturation to image anaerobic organisms and tumor core, and do not generate hydrogen peroxide. The small Ultra-Red Fluorescent Protein (smURFP) was evolved from a cyanobacterial phycobiliprotein to covalently attach biliverdin as an exogenous fluorophore. The small Ultra-Red Fluorescent Protein is biophysically as bright as the enhanced green fluorescent protein, is exceptionally photostable, used for biosensor development, and visible in living mice. Novel applications of smURFP include in vitro protein diagnostics with attomolar (10−18 M) sensitivity, encapsulation in viral particles, and fluorescent protein nanoparticles. However, the availability of biliverdin limits the fluorescence of biliverdin-attaching fluorescent proteins; hence, extra biliverdin is needed to enhance brightness. New methods for improved biliverdin bioavailability are necessary to develop improved bright far-red and near-infrared fluorescent proteins for noninvasive imaging in vivo.

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