The Agglomeration State of Nanoparticles Can Influence the Mechanism of Their Cellular Internalisation

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2017 Jun 28

PMID 28651541

Citations 25

Authors

Blanka Halamoda-Kenzaoui

Mara Ceridono

Patricia Urban

Alessia Bogni

Jessica Ponti

Sabrina Gioria

Agnieszka Kinsner-Ovaskainen

Affiliations

Soon will be listed here.

Abstract

Background: Significant progress of nanotechnology, including in particular biomedical and pharmaceutical applications, has resulted in a high number of studies describing the biological effects of nanomaterials. Moreover, a determination of so-called "critical quality attributes", that is specific physicochemical properties of nanomaterials triggering the observed biological response, has been recognised as crucial for the evaluation and design of novel safe and efficacious therapeutics. In the context of in vitro studies, a thorough physicochemical characterisation of nanoparticles (NPs), also in the biological medium, is necessary to allow a correlation with a cellular response. Following this concept, we examined whether the main and frequently reported characteristics of NPs such as size and the agglomeration state can influence the level and the mechanism of NP cellular internalization.

Results: We employed fluorescently-labelled 30 and 80 nm silicon dioxide NPs, both in agglomerated and non-agglomerated form. Using flow cytometry, transmission electron microscopy, the inhibitors of endocytosis and gene silencing we determined the most probable routes of cellular uptake for each form of tested silica NPs. We observed differences in cellular uptake depending on the size and the agglomeration state of NPs. Caveolae-mediated endocytosis was implicated particularly in the internalisation of well dispersed silica NPs but with an increase of the agglomeration state of NPs a combination of endocytic pathways with a predominant role of macropinocytosis was noted.

Conclusions: We demonstrated that the agglomeration state of NPs is an important factor influencing the level of cell uptake and the mechanism of endocytosis of silica NPs.

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References

Dharmawardhane S, Schurmann A, Sells M, Chernoff J, Schmid S, Bokoch G . Regulation of macropinocytosis by p21-activated kinase-1. Mol Biol Cell. 2000; 11(10):3341-52. PMC: 14996. DOI: 10.1091/mbc.11.10.3341. View

Pfeffer S . Caveolae on the move. Nat Cell Biol. 2001; 3(5):E108-10. DOI: 10.1038/35074625. View

Sundaramoorthy P, Ramasamy T, Mishra S, Jeong K, Yong C, Kim J . Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells. Acta Biomater. 2016; 42:220-231. DOI: 10.1016/j.actbio.2016.07.006. View

Pustylnikov S, Sagar D, Jain P, Khan Z . Targeting the C-type lectins-mediated host-pathogen interactions with dextran. J Pharm Pharm Sci. 2014; 17(3):371-92. PMC: 5553543. DOI: 10.18433/j3n590. View

Dos Santos T, Varela J, Lynch I, Salvati A, Dawson K . Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines. PLoS One. 2011; 6(9):e24438. PMC: 3176276. DOI: 10.1371/journal.pone.0024438. View

Slowing I, Vivero-Escoto J, Wu C, Lin V . Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev. 2008; 60(11):1278-1288. DOI: 10.1016/j.addr.2008.03.012. View

Vercauteren D, Vandenbroucke R, Jones A, Rejman J, Demeester J, De Smedt S . The use of inhibitors to study endocytic pathways of gene carriers: optimization and pitfalls. Mol Ther. 2009; 18(3):561-9. PMC: 2839427. DOI: 10.1038/mt.2009.281. View

Gratton S, Ropp P, Pohlhaus P, Luft J, Madden V, Napier M . The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A. 2008; 105(33):11613-8. PMC: 2575324. DOI: 10.1073/pnas.0801763105. View

Vranic S, Boggetto N, Contremoulins V, Mornet S, Reinhardt N, Marano F . Deciphering the mechanisms of cellular uptake of engineered nanoparticles by accurate evaluation of internalization using imaging flow cytometry. Part Fibre Toxicol. 2013; 10:2. PMC: 3599262. DOI: 10.1186/1743-8977-10-2. View

10.

Al Soraj M, He L, Peynshaert K, Cousaert J, Vercauteren D, Braeckmans K . siRNA and pharmacological inhibition of endocytic pathways to characterize the differential role of macropinocytosis and the actin cytoskeleton on cellular uptake of dextran and cationic cell penetrating peptides octaarginine (R8) and HIV-Tat. J Control Release. 2012; 161(1):132-41. DOI: 10.1016/j.jconrel.2012.03.015. View

11.

Ivanov A . Pharmacological inhibition of endocytic pathways: is it specific enough to be useful?. Methods Mol Biol. 2008; 440:15-33. DOI: 10.1007/978-1-59745-178-9_2. View

12.

Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y . Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small. 2011; 7(10):1322-37. DOI: 10.1002/smll.201100001. View

13.

Herd H, Daum N, Jones A, Huwer H, Ghandehari H, Lehr C . Nanoparticle geometry and surface orientation influence mode of cellular uptake. ACS Nano. 2013; 7(3):1961-73. PMC: 3860363. DOI: 10.1021/nn304439f. View

14.

Bitar A, Ahmad N, Fessi H, Elaissari A . Silica-based nanoparticles for biomedical applications. Drug Discov Today. 2012; 17(19-20):1147-54. DOI: 10.1016/j.drudis.2012.06.014. View

15.

Zielinski J, Moller A, Frenz M, Mevissen M . Evaluation of endocytosis of silica particles used in biodegradable implants in the brain. Nanomedicine. 2016; 12(6):1603-13. DOI: 10.1016/j.nano.2016.02.009. View

16.

Falcone S, Cocucci E, Podini P, Kirchhausen T, Clementi E, Meldolesi J . Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events. J Cell Sci. 2006; 119(Pt 22):4758-69. DOI: 10.1242/jcs.03238. View

17.

Kerr M, Teasdale R . Defining macropinocytosis. Traffic. 2009; 10(4):364-71. DOI: 10.1111/j.1600-0854.2009.00878.x. View

18.

Elkin S, Lakoduk A, Schmid S . Endocytic pathways and endosomal trafficking: a primer. Wien Med Wochenschr. 2016; 166(7-8):196-204. PMC: 4873410. DOI: 10.1007/s10354-016-0432-7. View

19.

Gold S, Monaghan P, Mertens P, Jackson T . A clathrin independent macropinocytosis-like entry mechanism used by bluetongue virus-1 during infection of BHK cells. PLoS One. 2010; 5(6):e11360. PMC: 2894058. DOI: 10.1371/journal.pone.0011360. View

20.

Reix N, Parat A, Seyfritz E, Van der Werf R, Epure V, Ebel N . In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles. Int J Pharm. 2012; 437(1-2):213-20. DOI: 10.1016/j.ijpharm.2012.08.024. View