Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; Harris, Georgina; Pamies, David; Santos, Lísia Maria Gobbo dos; Granjeiro, José Mauro; Högberg, Helena T.; Hartung, Thomas; Smirnova, Lena

doi:10.1186/s12989-019-0307-3

Cited by 73 publications

(60 citation statements)

References 114 publications

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“…AuNPs' desirable physicochemical properties comprise very small size, easy surface functionalization, as well as electrical and optical effects. Moreover, they allow surface functionalization based on several molecule types such as drugs, proteins and nucleic acids [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells

et al. 2020

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The aim of the current study is to present a strategy to improve the efficiency of 5-fluorouracil (5-FU), which is widely used as antineoplastic agent against solid tumors-based on the use of gold nanocarriers to overcome the resistance of colorectal cancer cells. 5-FU was loaded on gold nanoparticles (AuNP) coated with anti-EGFR antibodies in order to target them towards colorectal cancer cells that overexpress epidermal growth factor receptors (EGFR). Physicochemical characterization has shown that AuNP size was approximately 20 nm and that AuNP functionalization led to spherical nanoparticles. Flow cytometry allowed observing that some compounds synthesized by our research group have induced apoptosis/necrosis and impaired the proliferation of colon cancer cell lines ‘HCT-116′ and ‘HT-29′. The antibody/drug combination in AuNP (AuNP 5FU EGFR) has improved the apoptosis rate and impaired cell proliferation in both cell lines, regardless of the exposure time. Overall, these results have shown that AuNP functionalization with monoclonal antibodies focused on delivering 5-FU to tumor cells is an exciting strategy against colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells

et al. 2020

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“…With the aim of overcoming this gap, 3D models that better mimic the in vivo microenvironment and the interactions between different tissues or cells have been developed in recent years, such as organoids or organ-on-a-chip devices. These models can be manipulated to simulate different CNS diseases and, in this way, they can help to better predict NPs' effectiveness and biocompatibility [254,255]. Moreover, these models can be used to study disease progression and predict, for example, overexpressed receptors to be explored as targets, or the best time for the success of the strategy.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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“…NPs are now increasingly being used in theranostic applications, an emerging field in medicine that combines targeted therapies with disease monitoring (Scialabba et al, 2019). The importance of these applications has prompted the development of new platforms to screen for delivery efficiency in tissues, and organoids are playing an increasingly important role here as biomimetic disease models (Davoudi et al, 2018;Leite et al, 2019). The functions that NPs can play in a biological setting are constantly being expanded, with mechanical stimulation of matrices and tissues figuring prominently as an important new application area.…”

Section: Nps For Mechanical Stress Modulationmentioning

confidence: 99%

Nanoparticles as Versatile Tools for Mechanotransduction in Tissues and Organoids

Fattah

Ranga

2020

Front. Bioeng. Biotechnol.

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Organoids are 3D multicellular constructs that rely on self-organized cell differentiation, patterning and morphogenesis to recapitulate key features of the form and function of tissues and organs of interest. Dynamic changes in these systems are orchestrated by biochemical and mechanical microenvironments, which can be engineered and manipulated to probe their role in developmental and disease mechanisms. In particular, the in vitro investigation of mechanical cues has been the focus of recent research, where mechanical manipulations imparting local as well as large-scale mechanical stresses aim to mimic in vivo tissue deformations which occur through proliferation, folding, invagination, and elongation. However, current in vitro approaches largely impose homogeneous mechanical changes via a host matrix and lack the required positional and directional specificity to mimic the diversity of in vivo scenarios. Thus, while organoids exhibit limited aspects of in vivo morphogenetic events, how local forces are coordinated to enable large-scale changes in tissue architecture remains a difficult question to address using current techniques. Nanoparticles, through their efficient internalization by cells and dispersion through extracellular matrices, have the ability to provide local or global, as well as passive or active modulation of mechanical stresses on organoids and tissues. In this review, we explore how nanoparticles can be used to manipulate matrix and tissue mechanics, and highlight their potential as tools for fate regulation through mechanotransduction in multicellular model systems.

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Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery

Cited by 73 publications

References 114 publications

Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells

Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Nanoparticles as Versatile Tools for Mechanotransduction in Tissues and Organoids

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