Dataset Information

MnO₂-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

ABSTRACT: Multifunctional nanomaterials combining diagnosis and therapeutic properties have attracted a considerable attention in cancer research. Yet some important challenges are still to be faced, including an optimal coupling between these two types of properties that would be effective within complex biological tissues. To address these points, we have prepared novel nanoplatforms associating controlled drug delivery of doxorubicin and Magnetic Resonance Imaging (MRI) contrast-enhancement that exhibit high specificity towards cancer cells compared to normal cells and evaluated them both in 2D cultures and within 3D tissue-like biomimetic matrices.

Methods

Nanoplatforms were prepared from hollow silica nanoparticles coated with MnO₂ nanosheets and conjugated with the AS1411 aptamer as a targeting agent. They were fully characterized from a chemical and structural point of view as well as for drug release and MRI signal enhancement. Standard two-dimensional monolayer cultures were performed using HeLa and Normal Human Dermal Fibroblasts (NHDF) cells to testify targeting and cytotoxicity. Cellularized type I collagen-based hydrogels were also used to study nanoparticles behavior in 3D biomimetic environments.

Results

The as-established nanoplatforms can enter HeLa cells, leading to the dissociation of the MnO₂ nanosheets into Mn²⁺ that enhanced T₁ magnetic resonance signals and concomitantly release doxorubicin, both effects being markedly more significant than in the presence of NHDFs. Moreover, particles functionality and specificity were preserved when the cells were immobilized within type I collagen-based fibrillar hydrogels.

Conclusion

The use of MnO₂ nanosheets as glutathione-sensitive coatings of drug loaded nanoparticles together with surface conjugation with a targeting aptamer offers an effective strategy to obtain efficient and specific nanotheranostic systems for cancer research, both in 2D and 3D. The here-described tissue-like models should be easy to implement and could constitute an interesting intermediate validation step for newly-developed theranostic nanoparticles before in vivo evaluation.

SUBMITTER: Shi Y

PROVIDER: S-EPMC6170331 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

MnO<sub>2</sub>-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

Shi Yupeng Y Guenneau Flavien F Wang Xiaolin X Hélary Christophe C Coradin Thibaud T

Nanotheranostics 20180921 4

Multifunctional nanomaterials combining diagnosis and therapeutic properties have attracted a considerable attention in cancer research. Yet some important challenges are still to be faced, including an optimal coupling between these two types of properties that would be effective within complex biological tissues. To address these points, we have prepared novel nanoplatforms associating controlled drug delivery of doxorubicin and Magnetic Resonance Imaging (MRI) contrast-enhancement that exhibi ...[more]

PMID: 30324085

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Project description:IntroductionDuring the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood.MethodsGAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure.ResultsIn the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p < 0.001), respectively.ConclusionsThis work demonstrates that the proposed GAMER MRI might be a useful method to assess the relative importance of MRI measures in neurological diseases with focal pathology. Moreover, the obtained AWs may in fact help to choose the best combination of MR contrasts for a specific classification problem.

Dataset Information

MnO₂-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

Methods

Results

Conclusion

Publications

MnO<sub>2</sub>-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

MnO2-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

Methods

Results

Conclusion

Publications

MnO<sub>2</sub>-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

MnO₂-gated Nanoplatforms with Targeted Controlled Drug Release and Contrast-Enhanced MRI Properties: from 2D Cell Culture to 3D Biomimetic Hydrogels.