Tumor-on-Chip: Simulation of Complex Transport Around Tumor

2013 ◽  
Author(s):  
Bongseop Kwak ◽  
Kinam Park ◽  
Bumsoo Han
Keyword(s):  
Animal Models ◽  
Targeted Delivery ◽  
Fluid Pressure ◽  
Drug Carriers ◽  
Microfluidic System ◽  
Tissue Interactions ◽  
Transport Barriers ◽  
In Vitro Cell Cultures

Nanoparticles (NP) offer great potential as drug carriers for targeted delivery to tumor by increasing the delivery efficacy and reducing non-specific accumulation at non-targeted sites [1]. Despite these promising early outcomes [2], the NP delivery to target tumor site is still significantly limited due to complex in vivo transport barriers [3–5]. In order to improve the in vivo delivery efficacy, the NPs should be designed considering all these complex transport barriers beyond currently used enhanced permeation and retention (EPR) effect [6]. However, testing of NP delivery are primarily based on simple 2D or 3D in vitro cell cultures or animal models. However, these static 2D or 3D tumor models oversimplify the actual in vivo tumor environment including the absence of tissue-tissue interactions such as blood-endothelium, endothelium-intersititum, high interstitial fluid pressure, and interstitium-lymphatics [2, 3]. The animal models can provide the testbed with these tissue-tissue interactions, but it is very difficult to establish quantitative understanding of the NP transport at these tissue-tissue interfaces. To address these challenges and bridge the in vitro static models with the animal models, here we developed a 3D multi-layered microfluidic system that mimics the tissue-tissue interactions at tumor microenvironment is developed. The system is then used to investigate the transvascular and interstitial transport of NPs in tumor.

scholarly journals Lipid Nanostructured Particles as Emerging Carriers for Targeted Delivery of Bioactive Molecules: Applications in Food and Biomedical Sciences (An Overview)

2020 ◽  
Vol 77 (1) ◽  
pp. 37
Author(s):  
Patricia MUNTEAN ◽  
Carmen SOCACIU ◽  
Mihai Adrian SOCACIU
Keyword(s):  
Targeted Delivery ◽  
Drug Carriers ◽  
Lipid Nanoparticles ◽  
Bioactive Molecules ◽  
Biomedical Sciences ◽  
Nanostructured Particles ◽  
Drug Conjugates ◽  
Carrier Systems

Lipid nanoparticles are getting a growing scientific and technological interest, worldwide. Either Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), Lipid Drug Conjugates (LDCs) or Polymer-Lipid Nanoparticles (PLNs) have been produced and investigated last years, being reccomended as emerging carrier systems for many food and biomedical applications. An overview of the last publications, mainly since 2017 is presented, underlying the most important methods and techniques used for their preparation (e.g. high shear homogenization in hot and cold conditions, ultrasound assisted melt emulsification) as well techniques applied for measuring the size, calorimetric properties, zeta-potential, etc. Most relevant data related to the use of food-grade ingredients and designed lipid nanoparticles as delivery systems for organic and inorganic bioactive molecules in food or packaging’s are presented. The major reason for this trend in food science is the aim to overcome problems associated with the low bioavailability of many lipophilic bioactive compounds which are claimed to bring benefits to human health (carotenoid or anthocyanin pigments, sterols, vitamins). Finally, the recent applications of different formulas of lipid nanoparticles as drug carriers for in vitro experiments or for in vivo therapy (oral, parenteral or transdermal formulas) are presented.

Toxicity Effects of Anthracycline-Converted Herceptin and Azo-Functionalized Fe3O4 Nanoparticles on the Heart of Patients with Breast Cancer Based on Echocardiography

2021 ◽  
Vol 21 (2) ◽  
pp. 878-885
Author(s):  
Li Liu ◽  
Tingting Shen ◽  
Hongfang Liu ◽  
Gen Zhang ◽  
Yongfu Shao
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Combined Therapy ◽  
Drug Carriers ◽  
Temperature Sensitive ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Low Toxicity

The multifunctional nano-carrier system can simultaneously achieve multiple functions such as diagnostic imaging, targeted delivery of anti-tumor drugs, and combined therapy. Application potential Fe3O4 magnetic nanoparticles have the characteristics of low toxicity, superparamagnetism and good photothermal properties. Therefore, a multifunctional magnetic nanocarrier with both magnetic targeting and photothermal properties can be prepared by surface modification of Fe3O4 o DOX is an anti-tumor drug widely used in clinical treatment, and its severe toxic and side effects greatly limit its application. In this paper, a temperature-sensitive magnetic nanocarrier was first constructed and proved to have good superparamagnetism, photothermal properties, and biocom-patibility Then, Fe3O4-Azo-DOX drug-loaded nanoparticles were constructed by covalently bonding DOX. The prepared Fe3O4-Azo-DOX nanoparticles have high stability, sensitive photothermal response and low toxicity. Finally, Fe3O4-Azo-DOX was applied to the study of combined photother-motherapy and chemotherapy in vitro and in vivo. Based on Fe3O4 nanoparticles, a temperature-sensitive Fe3O4-Azo nanocarrier was constructed and its related properties were characterized. Furthermore, anthracycline nanodrugs were used in chemotherapy of breast cancer patients, and their effects were analyzed according to echocardiography parameter change. The results show that Fe3O4-Azo nanoparticles have a good photothermal heating effect. MCF-7 breast cancer cells were selected as a model to investigate the cytotoxicity of Fe3O4-Azo. The results proved that they have excellent biocompatibility and can be used as drug carriers. A Fe3O4-Azo nanocarrier was used to load DOX to construct a NIR-responsive nano-drug delivery system. By studying the NIR controlled release of Fe3O4-Azo-DOX under different pH conditions, it can be seen that it has NIR-responsive release function and the best release effect at pH 5.7. It was found that LVEF, LVFS, and E/A were significantly lower after chemotherapy than before (P < 0.05), which had a certain clinical value in cardiotoxicity The in vitro antitumor effect of Fe3O4-Azo-DOX was studied, and the results showed that the combined effect of photothermal-chemotherapy was significantly better than the photothermal treatment based on Fe3O4-Azo carrier alone and the chemotherapy based on free DOX alone.

scholarly journals Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chang Xue ◽  
Shuyao Hu ◽  
Zhi-Hua Gao ◽  
Lei Wang ◽  
Meng-Xue Luo ◽  
...  
Keyword(s):  
Gold Nanoparticle ◽  
Targeted Delivery ◽  
Target Genes ◽  
Sirna Delivery ◽  
Three Dimensional ◽  
Drug Carriers ◽  
High Serum ◽  
Exterior Surface

AbstractSmall interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Transplantation of Adipose-derived Cells for Periodontal Regeneration: A Systematic Review

2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Platelet Rich Plasma ◽  
Periodontal Regeneration ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Cell Sources ◽  
Study Designs

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models

mAbs ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1954136
Author(s):  
Sujatha Kumar ◽  
Srimoyee Ghosh ◽  
Geeta Sharma ◽  
Zebin Wang ◽  
Marilyn R. Kehry ◽  
...  
Keyword(s):  
Animal Models ◽  
Immune Function ◽  
Cellular Assays ◽  
In Vivo Animal Models

scholarly journals Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

2021 ◽  
Vol 7 (2) ◽  
pp. 113
Author(s):  
Anne-Laure Bidaud ◽  
Patrick Schwarz ◽  
Guillaume Herbreteau ◽  
Eric Dannaoui
Keyword(s):  
Animal Models ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Adequate Treatment ◽  
Combination Treatments ◽  
Target Organs ◽  
Fungal Load ◽  
Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

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