Evaluation of low-intensity pulsed ultrasound on doxorubicin delivery in 2D and 3D cancer cell cultures

Paškevičiūtė, Miglė; Januškevičienė, Indrė; Sakalauskienė, Kristina; Raišutis, Renaldas; Petrikaitė, Vilma

doi:10.1038/s41598-020-73204-y

Cited by 12 publications

(22 citation statements)

References 27 publications

(30 reference statements)

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“…According to Paškevičiūtė et al, 2020, US has no impact on the viability of MDA-MB-231 triple-negative breast cancer cells or A549 non-small cell lung cancer cells [9]. In line with these results, we did not detect any significant cytotoxicity effect at the single US treatment up to 2 minutes of US exposure.…”

Section: Us Probe Presents Cytotoxicity Towards Gbm and Epidermoid Ca...supporting

confidence: 85%

“…The therapeutic applications of ultrasound fall into two categories: non-destructive mechanical heating of tissue to trigger the natural physiological response to injury, as well as for selective destruction of target tissues and organs to enhance efficacy and selectivity [13]. Due to these beneficial biological interactions, US has developed a rising interest in the subject of drug delivery in recent decades [9]. US has been investigated in clinical studies for the transitory opening of the BBB, with trials to far proving the approach's safety and viability [14][15][16]; it has emerged as a safe, feasible strategy for non-invasively, locally, and reversibly opening the BBB [8,17,18].…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Wanigasekara,

Mondala,

Cullen

et al. 2023

Preprint

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A myriad of biological effects can be stimulated by the ultrasound (US) for the treatment of cancer. The objective of our research was to investigate the effect of ultrasound alone and in combination with the chemotherapeutic drugs such as doxorubicin (DOX) and temozolomide (TMZ) on human glioblastoma (GBM) and the human epidermoid carcinoma cancer 2D and 3D cell cultures. Results indicated that the US 96-probe device could induce tumour sphere cytotoxicity in a dosage- and time-dependent manner, with multiple treatments augmenting this cytotoxic effect. With enhanced cytotoxicity, US decreased tumour sphere growth metabolic activity, disrupted spheroid integrity, and heightened the occurrence of DNA double strand breaks, resulting in damage to tumour spheres and an inability to rebuild tumour spheres after multiple US treatments. The combination of US and TMZ/DOX enhanced the efficiency of treatment for GBM and epidermoid carcinoma by enhancing induced cytotoxicity in 3D tumour spheres compared to 2D monolayer cells, and also by increasing the incubation time, which is the most crucial way to differentiate between the effectiveness of drug treatment with and without US. In conclusion, our data demonstrate that US enhances drug diffusion, uptake, and cytotoxicity using 3D spheroid models when compared with 2D cultures. It also demonstrates the significance of 3D cell culture models in drug delivery and discovery research.

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Section: Us Probe Presents Cytotoxicity Towards Gbm and Epidermoid Ca...supporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Wanigasekara,

Mondala,

Cullen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…To overcome this issue, Dox is either actively administered in free form using drug delivery methods or encapsulated inside pegylated liposomes (Doxil ® or Caelyx ® ) or polymeric nanoparticles, which can be passively administered but also actively delivered. Thus, Paškevičiūtė et al [ 68 ] evaluated the influence of MB-assisted US on the delivery of doxorubicin (Dox) into monolayer cells and MCTS of triple-negative breast cancer (MDA-MB-231) or non-small-cell lung cancer (NSCLC) (A549) cells cocultured with human fibroblasts. MCTSs were formed using a magnetic 3D bioprinting method.…”

Section: Resultsmentioning

confidence: 99%

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

et al. 2023

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Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acoustically mediated drug therapies. We discuss the limitations of the current studies and future perspectives. Various spheroid formation methods enable the easy and reproducible generation of spheroids and MCTSs. The development and assessment of acoustically mediated drug therapies have been mainly demonstrated in spheroids made up of tumor cells only. Despite the promising results obtained with these spheroids, the successful evaluation of these therapies will need to be addressed in more relevant 3D vascular MCTS models using MCTS-on-chip platforms. These MTCSs will be generated from patient-derived cancer cells and nontumor cells, such as fibroblasts, adipocytes, and immune cells.

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“…In the previous studies using BC cell lines and mainly 3D spheroid bioprinting, the authors described the growth characteristics, size and shape distribution [67] of the spheroids (live/dead cell ratio measured by different assays) and analysed some protein expressions (MMPs, EMT markers, stem cell markers, integrins, cell-cell connections, and matrix depositions) [58,[68][69][70] or certain drug sensitivities (e.g., doxorubicin, paclitaxel, and 5-FU). In the case of doxorubicin treatment, maintained or decreased sensitivity were documented in 3D culture conditions [36,37,49,60,[69][70][71][72]. These contradictions can be explained by the limitations of the used proliferation/viability assays, cell types and the differences between the used cell line and 3D culturing techniques in previous studies.…”

Section: Discussionmentioning

confidence: 98%

“…The number of developments related to the organ-on-chip technique is increasing in many tumour types, including colon cancers, gliomas, breast cancers, osteosarcomas, lung cancers, etc. [65,[68][69][70][71][72]. Modelling the complexity of tumour progression, especially the steps of metastasis formation, also requires microfluidics and several host tissues to be combined in novel in vitro test systems [82][83][84][85][86][87][88][89][90][91][92][93].…”

Section: Discussionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

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Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.

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Evaluation of low-intensity pulsed ultrasound on doxorubicin delivery in 2D and 3D cancer cell cultures

Cited by 12 publications

References 27 publications

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

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