Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo

Rinkenauer, Alexandra C.; Press, Adrian T.; Raasch, Martin; Pietsch, Christian; Schweizer, Simon; Schwörer, Simon; Rudolph, K. Lenhard; Mosig, Alexander S.; Bauer, Michael; Traeger, Anja; Schubert, Ulrich S.

doi:10.1016/j.jconrel.2015.08.008

Cited by 39 publications

(39 citation statements)

References 60 publications

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“…Collectively, these features may negatively affect endothelial cell growth and viability at concentrations of 100 μg/ml and higher. Moreover, the recently reported data as well as our present studies indicate that physiologic flow is one of the important factors that must be considered when designing drug delivery nanosystems, as the internalization of untargeted nanoparticles by endothelial cells differs greatly between static and dynamic conditions [34][35][36].…”

Section: Io-np2supporting

confidence: 57%

“…Whereas laminar flow protects endothelial cells from harmful stimuli, nonuniform shear stress induces endothelial activation [31]. Furthermore, recent studies showed that the endothelial uptake on untargeted nanoparticles greatly depends on the presence and magnitude of shear stress [34][35][36]. Therefore, experiments under flow conditions are necessary to estimate the cell responses in physiological-like settings.…”

Section: Nanoparticle Effects On Ecs In Dynamic Cell Culture Conditionsmentioning

confidence: 99%

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Nanoparticles for Intravascular Applications: Physicochemical Characterization and Cytotoxicity Testing

Matuszak

Baumgartner

Zaloga

et al. 2016

Nanomedicine (Lond.)

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Aim:We report the physicochemical analysis of nanosystems intended for cardiovascular applications and their toxicological characterization in static and dynamic cell culture conditions. Methods: Size, polydispersity and ζ-potential were determined in 10 nanoparticle systems including liposomes, lipid nanoparticles, polymeric and iron oxide nanoparticles. Nanoparticle effects on primary human endothelial cell viability were monitored using real-time cell analysis and live-cell microscopy in static conditions, and in a flow model of arterial bifurcations. Results & conclusions: The majority of tested nanosystems were well tolerated by endothelial cells up to the concentration of 100 μg/ml in static, and up to 400 μg/ml in dynamic conditions. Pilot experiments in a pig model showed that intravenous administration of liposomal nanoparticles did not evoke the hypersensitivity reaction. These findings are of importance for future clinical use of nanosystems intended for intravascular applications.

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Section: Io-np2supporting

confidence: 57%

Section: Nanoparticle Effects On Ecs In Dynamic Cell Culture Conditionsmentioning

confidence: 99%

Nanoparticles for Intravascular Applications: Physicochemical Characterization and Cytotoxicity Testing

Matuszak

Baumgartner

Zaloga

et al. 2016

Nanomedicine (Lond.)

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“…In this respect, we should consider that one of the major limitations of drug delivery nanosystems is their fast uptake by the reticuloendothelial system (RES), which consists of phagocytic cells such as monocytes and macrophages, including liver Kupffer cells, resulting in short circulation half-lives of nanosystems. [42][43][44] However, our anionic nanosystems demonstrated in vivo LSEC-specific internalization, avoiding Kupffer cell uptake.…”

Section: Discussionmentioning

confidence: 87%

Targeting liver sinusoidal endothelial cells with miR‐20a‐loaded nanoparticles reduces murine colon cancer metastasis to the liver

Márquez

Fernandez-Piñeiro

Araúzo-Bravo

et al. 2018

Intl Journal of Cancer

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Phenotypic transformation of liver sinusoidal endothelial cells is one of the most important stages of liver metastasis progression. The miRNA effects on liver sinusoidal endothelial cells during liver metastasis have not yet been studied. Herein, whole genome analysis of miRNA expression in these cells during colorectal liver metastasis revealed repressed expression of microRNA-20a. Importantly, downregulation of miR-20a occurs in parallel with upregulation of its known protein targets. To restore normal miR-20a levels in liver sinusoidal endothelial cells, we developed chondroitin sulfate-sorbitan ester nanoparticles conjugated with miR-20a in a delivery system that specifically targets liver sinusoidal endothelial cells. The restoration of normal mir-20a levels in these cells induced downregulation of the expression of its protein targets, and this also resulted in a reduction of in vitro LSEC migration and a reduction of in vivo activation and tumor-infiltrating capacity and ability of the tumor decreased by ∼80% in a murine liver metastasis model.

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“…These polymer-grafted gold nanoparticles were prepared in one step, via a direct method using polymer ligands obtained by controlled radical polymerization 33 and previously proved to ensure nanoparticle biocompatibility and enhanced cellular uptake. 34 The behavior of the synthesized nano-objects has been extensively characterized before and under irradiation. 33 It was particularly shown that PMAA-AuNPs can safely withstand doses higher than 300 Gy, which is the maximum dose achieved in radioiodine treatment.…”

Section: Introductionmentioning

confidence: 99%

<p>Improving <sup>131</sup>I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

Goas¹,

Paquet²,

Paquirissamy³

et al. 2019

IJN

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Background: Human trials combining external radiotherapy (RT) and metallic nanoparticles are currently underway in cancer patients. For internal RT, in which a radioisotope such as radioiodine is systemically administered into patients, there is also a need for enhancing treatment efficacy, decreasing radiation-induced side effects and overcoming radio-resistance. However, if strategies vectorising radioiodine through nanocarriers have been documented, sensitizing the neoplasm through the use of nanotherapeutics easily translatable to the clinic in combination with the standard systemic radioiodine treatment has not been assessed yet. Method and materials: The present study explored the potential of hybrid poly (methacrylic acid)-grafted gold nanoparticles to improve the performances of systemic 131 I-mediated RT on cancer cells and in tumor-bearing mice. Such nanoparticles were chosen based on their ability previously described by our group to safely withstand irradiation doses while exhibiting good biocompatibility and enhanced cellular uptake. Results: In vitro clonogenic assays performed on melanoma and colorectal cancer cells showed that poly(methacrylic acid)-grafted gold nanoparticles (PMAA-AuNPs) could efficiently lead to a marked tumor cell mortality when combined to a low activity of radioiodine, which alone appeared to be essentially ineffective on tumor cells. In vivo, tumor enrichment with PMAA-AuNPs significantly enhanced the killing potential of a systemic radioiodine treatment. Conclusion: This is the first report of a simple and reliable nanomedicine-based approach to reduce the dose of radioiodine required to reach curability. In addition, these results open up novel perspectives for using high-Z metallic NPs in additional molecular radiation therapy demonstrating heterogeneous dose distributions.

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Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo

Cited by 39 publications

References 60 publications

Nanoparticles for Intravascular Applications: Physicochemical Characterization and Cytotoxicity Testing

Nanoparticles for Intravascular Applications: Physicochemical Characterization and Cytotoxicity Testing

Targeting liver sinusoidal endothelial cells with miR‐20a‐loaded nanoparticles reduces murine colon cancer metastasis to the liver

<p>Improving <sup>131</sup>I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

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