Ultrastructural Features of Gold Nanoparticles Interaction with HepG2 and HEK293 Cells in Monolayer and Spheroids

Челобанов, Б. П.; Poletaeva, Yuliya; Epanchintseva, Anna V.; Tupitsyna, Anastasiya; Pyshnaya, I. A.; Ryabchikova, E. I.

doi:10.3390/nano10102040

Cited by 9 publications

(6 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An exploration of gold nanorods, nanospheres, and oligonucleotide-functionalized nanospheres was undertaken by Rane et al who showed the difference in uptake profiles present in a 3D model compared to the 2D monolayer [ 43 ]. Further studies on how functionalization and size of the GNPs have been explored recently, all agreeing that smaller GNPs will more effectively penetrate deeper into the cells [ 44 , 45 ]. More complex in vivo systems can also be reproduced in a spheroid model, such as a blood-brain barrier made up multiple cell types in a multicellular spheroid.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

Bromma

Alhussan

Monica

et al. 2021

Cancers

View full text Add to dashboard Cite

Radiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials, such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor environment compared to a two-dimensional (2D) monolayer model have been used. We tested the uptake of 15 nm GNPs and 50 nm GNPs on a monolayer and on spheroids of two cancer cell lines, CAL-27 and HeLa, to evaluate the differences between a 2D and 3D model in similar conditions. The anticancer drug docetaxel (DTX) which can act as a radiosensitizer, was also utilized, informing future potential of GNP-mediated combined therapeutics. In the 2D monolayer model, the addition of DTX induced a small, non-significant increase of uptake of GNPs of between 13% and 24%, while in the 3D spheroid model, DTX increased uptake by between 47% and 186%, with CAL-27 having a much larger increase relative to HeLa. Further, the depth of penetration of 15 nm GNPs over 50 nm GNPs increased by 33% for CAL-27 spheroids and 17% for HeLa spheroids. These results highlight the necessity to optimize GNP treatment conditions in a more realistic tumor-life environment. A 3D spheroid model can capture important details, such as different packing densities from different cancer cell lines, which are absent from a simple 2D monolayer model.

show abstract

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

Bromma

Alhussan

Monica

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…The materials in these studies are however encountered as bulk materials, assessed for occupational or environmental safety, and thus they are not NBMs developed for medical uses or medical technology, like the materials presented in this study. To date, very few publications have used 3D hepatocellular carcinoma models for assessing toxicity of NBMs, with most studies utilising spheroids to assess depth and penetrations of NBMs in 3D [73][74][75][76][77]. To the best of our knowledge, this study is the first time 3D liver spheroids have been used in the in vitro toxicity screening of these specific NBMs, making the work presented an advancement in the nanomedicine field.…”

Section: Discussionmentioning

confidence: 99%

Pre-clinical 2D and 3D toxicity response to a panel of nanomaterials; comparative assessment of NBM-induced liver toxicity

Tutty

Vella

Prina-Mello

2022

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

Nanobiomaterials, or NBMs, have been used in medicine and bioimaging for decades, with wide-reaching applications ranging from their uses as carriers of genes and drugs, to acting as sensors and probes. When developing nanomedicine products, it is vitally important to evaluate their safety, ensuring that both biocompatibility and efficacy are achieved so their applications in these areas can be safe and effective. When discussing the safety of nanomedicine in general terms, it is foolish to make generalised statements due to the vast array of different manufactured nanomaterials, formulated from a multitude of different materials, in many shapes and sizes; therefore, NBM pre-clinical screening can be a significant challenge. Outside of their distribution in the various tissues, organs and cells in the body, a key area of interest is the impact of NBMs on the liver. A considerable issue for researchers today is accurately predicting human-specific liver toxicity prior to clinical trials, with hepatotoxicity not only the most cited reasons for withdrawal of approved drugs, but also a primary cause of attrition in pre-launched drug candidates. To date, no simple solution to adequately predict these adverse effects exists prior to entering human experimentation. The limitations of the current pre-clinical toolkit are believed to be one of the main reasons for this, with questions being raised on the relevance of animal models in pre-clinical assessment, and over the ability of conventional, simplified in vitro cell–based assays to adequately assess new drug candidates or NBMs. Common 2D cell cultures are unable to adequately represent the functions of 3D tissues and their complex cell–cell and cell–matrix interactions, as well as differences found in diffusion and transport conditions. Therefore, testing NBM toxicity in conventional 2D models may not be an accurate reflection of the actual toxicity these materials impart on the body. One such method of overcoming these issues is the use of 3D cultures, such as cell spheroids, to more accurately assess NBM-tissue interaction. In this study, we introduce a 3D hepatocellular carcinoma model cultured from HepG2 cells to assess both the cytotoxicity and viability observed following treatment with a variety of NBMs, namely a nanostructured lipid carrier (in the specific technical name = LipImage™ 815), a gold nanoparticle (AuNP) and a panel of polymeric (in the specific technical name = PACA) NBMs. This model is also in compliance with the 3Rs policy of reduction, refinement and replacement in animal experimentation [1], and meets the critical need for more advanced in vitro models for pre-clinical nanotoxicity assessment. Graphical abstract Pipeline for the pre-clinical assessment of NBMs in liver spheroid model

show abstract

“…These materials however are ones which may been encountered occupationally and are not technically NBMs which can be applied to medical technology, like the materials presented in this study. To date, very few publications have used 3D liver models for assessing toxicity of NBMs, with most studies utilising spheroids to assess depth and penetrations of NBMs in 3D[49][50][51][52][53], and to the best of our knowledge this study in vitro toxicity screening, making the work presented in this work a signi cant advance in the eld.…”

mentioning

confidence: 99%

Pre-clinical 2D and 3D Toxicity Response to A Panel of Nanomaterials; Comparative Assessment of NBM-Induced Liver Toxicity

Tutty

Prina‐Mello

Vella

2022

Preprint

View full text Add to dashboard Cite

Nanobiomaterials, or NBMs, have been used in medicine and bioimaging for decades, with wide-reaching applications ranging from their uses as carriers of genes and drugs, to acting as sensors and probes. When developing nanomedicine products, it is vitally important to evaluate their safety, ensuring that both biocompatibility and efficacy are achieved so their applications in these areas can be safe and effective. When discussing the safety of nanomedicine in general terms, it is foolish to make generalized statements due to the vast array of different manufactured nanomaterials, formulated from a multitude of different materials, in many shapes and sizes, therefore NBM preclinical screening can be a significant challenge. Outside of their distribution in the various tissues, organs and cells in the body, a key area of interest is the impact of NBMs on the liver. A considerable issue for researchers today is accurately predicting human-specific liver toxicity prior to clinical trials, with hepatotoxicity not only the most cited reasons for withdrawal of approved drugs, but also a primary cause of attrition in pre-launch drug candidates. To date, no simple solution to adequately predict these adverse effects exist prior to entering human experimentation. The limitations of the current preclinical toolkit are believed to be one of the main reasons for this, with questions being raised on the relevance of animal models in pre-clinical assessment, and over the ability of conventional, simplified in vitro cell based assays to adequately assess new drug candidates or NBMs. Common 2D cell cultures are unable to adequately represent the functions of 3D tissues and their complex cell–cell and cell–matrix interactions, as well as differences found in diffusion and transport conditions. Therefore, testing NBM toxicity in conventional 2D models may not be an accurate reflection of the actual toxicity these materials impart on the body. One such method of overcoming these issues is the use of 3D cultures, such as cell spheroids, to more accurate assess NBM-tissue interaction. In this study, we introduce a 3D liver model cultured from HepG2 cells to assess both the cytotoxicity and viability observed following treatment with a variety of NBMs, namely a liposome (in the specific technical name = LipImage), a gold nanoparticle (AuNP) and a panel of polymeric (in the specific technical name = PACA) NBMs. This model is also in compliance with the 3Rs policy of reduction, refinement and replacement in animal experimentation [1], and meets the critical need for more advanced in vitro models for pre-clinical nanotoxicity assessment.

show abstract

Ultrastructural Features of Gold Nanoparticles Interaction with HepG2 and HEK293 Cells in Monolayer and Spheroids

Cited by 9 publications

References 65 publications

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

Pre-clinical 2D and 3D toxicity response to a panel of nanomaterials; comparative assessment of NBM-induced liver toxicity

Pre-clinical 2D and 3D Toxicity Response to A Panel of Nanomaterials; Comparative Assessment of NBM-Induced Liver Toxicity

Contact Info

Product

Resources

About