https://doi.org/10.4081/ejh.2022.3603
Assessing the interactions between nanoparticles and biological barriers in vitro: a new challenge for microscopy techniques in nanomedicine
Submitted: 11 November 2022
Accepted: 17 November 2022
Published: 24 November 2022
Accepted: 17 November 2022
Abstract Views: 445
PDF: 284
HTML: 15
HTML: 15
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Nanoconstructs intended to be used as biomedical tool must be assessed for their capability to cross biological barriers. However, studying in vivo the permeability of biological barriers to nanoparticles is quite difficult due to the many structural and functional factors involved. Therefore, the in vitro modeling of biological barriers -2D cell monocultures, 2D/3D cell co-cultures, microfluidic devices- is gaining more and more relevance in nanomedical research. Microscopy techniques play a crucial role in these studies, as they allow both visualizing nanoparticles inside the biological barrier and evaluating their impact on the barrier components. This paper provides an overview of the various microscopical approaches used to investigate nanoparticle translocation through in vitro biological barrier models. The high number of scientific articles reported highlights the great contribution of the morphological and histochemical approach to the knowledge of the dynamic interactions between nanoconstructs and the living environment.
Carton F, Malatesta M. In vitro models of biological barriers for nanomedical research. Int J Mol Sci 2022; 23:8910.
DOI: https://doi.org/10.3390/ijms23168910
Malatesta M, Giagnacovo M, Costanzo M, Conti B, Genta I, Dorati R, et al. Diaminobenzidine photoconversion is a suitable tool for tracking the intracellular location of fluorescently labelled nanoparticles at transmission electron microscopy. Eur J Histochem 2012;56:e20.
DOI: https://doi.org/10.4081/ejh.2012.20
Carton F, Repellin M, Lollo G, Malatesta M. Alcian blue staining to track the intracellular fate of hyaluronic-acid-based nanoparticles at transmission electron microscopy. Eur J Histochem 2019;63:3086.
DOI: https://doi.org/10.4081/ejh.2019.3086
Guglielmi V, Carton F, Vattemi G, Arpicco S, Stella B, Berlier G, et al. Uptake and intracellular distribution of different types of nanoparticles in primary human myoblasts and myotubes. Int J Pharm 2019;560:347-56.
DOI: https://doi.org/10.1016/j.ijpharm.2019.02.017
Kim D, Jeong K, Kwon JE, Park H, Lee S, Kim S, et al. Dual-color fluorescent nanoparticles showing perfect color-specific photoswitching for bioimaging and super-resolution microscopy. Nat Commun 2019;10:3089.
DOI: https://doi.org/10.1038/s41467-019-10986-4
Mannucci S, Boschi F, Cisterna B, Esposito E, Cortesi R, Nastruzzi C, et al. A Correlative imaging study of in vivo and ex vivo biodistribution of solid lipid nanoparticles. Int J Nanomedicine 2020;15:1745-58.
DOI: https://doi.org/10.2147/IJN.S236968
Costanzo M, Esposito E, Sguizzato M, Lacavalla MA, Drechsler M, Valacchi G, et al. Formulative study and intracellular fate evaluation of ethosomes and transethosomes for Vitamin D3 delivery. Int J Mol Sci 2021;22:5341.
DOI: https://doi.org/10.3390/ijms22105341
Malatesta M. Transmission electron microscopy as a powerful tool to investigate the interaction of nanoparticles with subcellular structures. Int J Mol Sci 2021;22:12789.
DOI: https://doi.org/10.3390/ijms222312789
Malatesta M. Histochemistry for nanomedicine: Novelty in tradition. Eur J Histochem 2021;65:3376.
DOI: https://doi.org/10.4081/ejh.2021.3376
Yang G, Liu Y, Zhao CX. Quantitative comparison of different fluorescent dye-loaded nanoparticles. Colloids Surf B Biointerfaces 2021;206:111923.
DOI: https://doi.org/10.1016/j.colsurfb.2021.111923
Cappellozza E, Boschi F, Sguizzato M, Esposito E, Cortesi R, Malatesta M, et al. A spectrofluorometric analysis to evaluate transcutaneous biodistribution of fluorescent nanoparticulate gel formulations. Eur J Histochem 2022;66:3321.
DOI: https://doi.org/10.4081/ejh.2022.3321
Li W, Kaminski Schierle GS, Lei B, Liu Y, Kaminski CF. Fluorescent nanoparticles for super-resolution imaging. Chem Rev 2022;122:12495-543.
DOI: https://doi.org/10.1021/acs.chemrev.2c00050
Bitonto V, Garello F, Scherberich A, Filippi M. Prussian Blue Staining to Visualize Iron Oxide Nanoparticles. Methods Mol Biol 2023;2566:321-32.
DOI: https://doi.org/10.1007/978-1-0716-2675-7_26
Cheli F, Falsini S, Salvatici MC, Ristori S, Schiff S, Corti E, et al. Fluorescent labeling of lignin nanocapsules with fluorol yellow 088. Methods Mol Biol 2023;2566:345-53.
DOI: https://doi.org/10.1007/978-1-0716-2675-7_28
Costanzo M, Malatesta M. Diaminobenzidine photooxidation to visualize fluorescent nanoparticles in adhering cultured cells at transmission electron microscopy. Methods Mol Biol 2023;2566:333-43.
DOI: https://doi.org/10.1007/978-1-0716-2675-7_27
Repellin M, Carton F, Lollo G, Malatesta M. Alcian Blue staining to visualize intracellular hyaluronic acid-based nanoparticles. Methods Mol Biol 2023;2566:313-30.
DOI: https://doi.org/10.1007/978-1-0716-2675-7_25
Matea CT, Mocan T, Tabaran F, Pop T, Mosteanu O, Puia C, et al. Quantum dots in imaging, drug delivery and sensor applications. Int J Nanomedicine 2017;12:5421-31.
DOI: https://doi.org/10.2147/IJN.S138624
Boruah A, Saikia BK. Synthesis, characterization, properties, and novel applications of fluorescent nanodiamonds. J Fluoresc 2022;32:863-85.
DOI: https://doi.org/10.1007/s10895-022-02898-2
Cardellini J, Balestri A, Montis C, Berti D. Advanced static and dynamic fluorescence microscopy techniques to investigate drug delivery systems. Pharmaceutics 2021;13:861.
DOI: https://doi.org/10.3390/pharmaceutics13060861
Kostarelos K, Emfietzoglou D, Papakostas A, Yang, WH, Ballangrud Å, Sgouros G. Binding and Interstitial penetration of liposomes within avascular tumor spheroids. Int J Cancer 2004;112:713–21.
DOI: https://doi.org/10.1002/ijc.20457
Wojnilowicz M, Besford QA, Wu YL, Loh XJ, Braunger JA, Glab A, et al. Glycogen-nucleic acid constructs for gene silencing in multicellular tumor spheroids. Biomaterials 2018;176:34-49.
DOI: https://doi.org/10.1016/j.biomaterials.2018.05.024
Sims LB, Huss MK, Frieboes HB, Steinbach-Rankins JM. Distribution of PLGA-modified nanoparticles in 3D cell culture models of hypo-vascularized tumor tissue. J Nanobiotechnol 2017;15:67.
DOI: https://doi.org/10.1186/s12951-017-0298-x
Xu X, Sabanayagam CR, Harrington DA, Farach-Carson MC, Jia X. A hydrogel-based tumor model for the evaluation of nanoparticle-based cancer therapeutics. Biomaterials 2014;35:3319-30.
DOI: https://doi.org/10.1016/j.biomaterials.2013.12.080
Le VM, Lang MD, Shi WB, Liu JW. A Collagen-based multicellular tumor spheroid model for evaluation of the efficiency of nanoparticle drug delivery. Artif Cells Nanomed Biotechnol 2016;44:540-4. doi:10.3109/21691401.2014.968820.
DOI: https://doi.org/10.3109/21691401.2014.968820
Wang HF, Ran R, Liu Y, Hui Y, Zeng B, Chen D, et al. Tumor-vasculature-on-a-chip for investigating nanoparticle extravasation and tumor accumulation. ACS Nano 2018;12:11600-9.
DOI: https://doi.org/10.1021/acsnano.8b06846
Paek J, Park SE, Lu Q, Park KT, Cho M, Oh JM, et al. Microphysiological engineering of self-assembled and perfusable microvascular beds for the production of vascularized three-dimensional human microtissues. ACS Nano 2019;13:7627-43.
DOI: https://doi.org/10.1021/acsnano.9b00686
Schuerle S, Soleimany AP, Yeh T, Anand GM, Häberli M, Fleming HE, et al. Synthetic and living micropropellers for convection-enhanced nanoparticle transport. Sci Adv 2019;5:eaav4803.
DOI: https://doi.org/10.1126/sciadv.aav4803
Bengalli R, Colantuoni A, Perelshtein I, Gedanken A, Collini M, Mantecca P, et al. In vitro skin toxicity of CuO and ZnO nanoparticles: Application in the safety assessment of antimicrobial coated textiles. NanoImpact 2021;21:100282.
DOI: https://doi.org/10.1016/j.impact.2020.100282
Kadiyala I, Loo Y, Roy K, Rice J, Leong KW. Transport of chitosan-DNA Nanoparticles in human intestinal M-cell Model versus normal intestinal enterocytes. Eur J Pharm Sci 2010;39:103-9.
DOI: https://doi.org/10.1016/j.ejps.2009.11.002
Gullberg E, Keita AV, Salim SY, Andersson M, Caldwell KD, Söderholm JD, et al. Identification of Cell adhesion molecules in the human follicle-associated epithelium that improve nanoparticle uptake into the Peyer’s patches. J Pharmacol Exp Ther 2006;319:632-9.
DOI: https://doi.org/10.1124/jpet.106.107847
Jin Y, Song Y, Zhu X, Zhou D, Chen C, Zhang Z, et al. Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. Biomaterials 2012;33:1573-82.
DOI: https://doi.org/10.1016/j.biomaterials.2011.10.075
Ma H, Jiang Q, Han S, Wu Y, Cui Tomshine J, Wang D, et al. Multicellular tumor spheroids as an in vivo-like tumor model for three-dimensional imaging of chemotherapeutic and nano material cellular penetration. Mol Imaging 2012;11:487–98.
DOI: https://doi.org/10.2310/7290.2012.00012
Gibot L, Lemelle A, Till U, Moukarzel B, Mingotaud AF, Pimienta V, et al. Polymeric micelles encapsulating photosensitizer: Structure/photodynamic therapy efficiency relation. Biomacromolecules 2014;15:1443-55.
DOI: https://doi.org/10.1021/bm5000407
George I, Vranic S, Boland S, Courtois A, Baeza-Squiban A. Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation. Toxicol In Vitro 2015;29:51-8.
DOI: https://doi.org/10.1016/j.tiv.2014.08.003
Schimpel C, Teubl B, Absenger M, Meindl C, Fröhlich E, Leitinger G, et al. Development of an advanced intestinal in vitro triple culture permeability model to study transport of nanoparticles. Mol Pharm 2014;11:808-18.
DOI: https://doi.org/10.1021/mp400507g
Da Silva-Candal A, Brown T, Krishnan V, Lopez-Loureiro I, Ávila-Gómez P, Pusuluri A, et al. Shape Effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions. J Control Release 2019;309:94-105.
DOI: https://doi.org/10.1016/j.jconrel.2019.07.026
Belli V, Guarnieri D, Biondi M, Della Sala F, Netti PA. Dynamics of nanoparticle diffusion and uptake in three-dimensional cell cultures. Colloids Surf B Biointerfaces 2017;149:7–15.
DOI: https://doi.org/10.1016/j.colsurfb.2016.09.046
Priwitaningrum DL, Blondé JBG, Sridhar A, van Baarlen J, Hennink WE, Storm G, et al. Tumor stroma-containing 3D Spheroid arrays: A Tool to study nanoparticle penetration. J Control Release 2016;244:257-68.
DOI: https://doi.org/10.1016/j.jconrel.2016.09.004
Albanese A, Lam AK, Sykes EA, Rocheleau JV, Chan WCW. Tumour-on-a-chip provides an optical window into nanoparticle tissue transport. Nat Commun 2013;4:2718.
DOI: https://doi.org/10.1038/ncomms3718
Chen Y, Gao D, Wang Y, Lin S, Jiang Y. A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems. Anal Chim Acta 2018;1036:97-106.
DOI: https://doi.org/10.1016/j.aca.2018.06.038
Huang K, Boerhan R, Liu C, Jiang G. Nanoparticles penetrate into the multicellular spheroid-on-chip: Effect of surface charge, protein corona, and exterior flow. Mol Pharm 2017;14:4618-27.
DOI: https://doi.org/10.1021/acs.molpharmaceut.7b00726
Cantisani M, Guarnieri D, Biondi M, Belli V, Profeta M, Raiola L, et al. Biocompatible nanoparticles sensing the matrix metallo-proteinase 2 for the on-demand release of anticancer drugs in 3D tumor spheroids. Colloids Surf B Biointerfaces 2015;135:707-16.
DOI: https://doi.org/10.1016/j.colsurfb.2015.08.016
Moreira AF, Dias DR, Costa EC, Correia IJ. Thermo- and PH-responsive nano-in-micro particles for combinatorial drug delivery to cancer cells. Eur J Pharm Sci 2017;104:42–51.
DOI: https://doi.org/10.1016/j.ejps.2017.03.033
Hou X, Liu S, Wang M, Wiraja C, Huang W, Chan P, et al. Layer-by-layer 3D constructs of fibroblasts in hydrogel for examining transdermal penetration capability of nanoparticles. SLAS Technol 2017;22:447-53.
DOI: https://doi.org/10.1177/2211068216655753
Papademetriou I, Vedula E, Charest J, Porter T. Effect of flow on targeting and penetration of angiopep-decorated nanoparticles in a microfluidic model blood-brain barrier. PLoS One 2018;13:e0205158.
DOI: https://doi.org/10.1371/journal.pone.0205158
Lee SWL, Campisi M, Osaki T, Possenti L, Mattu C, Adriani G, et al. Modeling nanocarrier transport across a 3D in vitro human blood-brain–barrier microvasculature. Adv Healthc Mater 2020;9:1901486.
DOI: https://doi.org/10.1002/adhm.201901486
Carvalho MR, Barata D, Teixeira LM, Giselbrecht S, Reis RL, Oliveira JM, et al. Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine. Sci Adv 2019;5:eaaw1317.
DOI: https://doi.org/10.1126/sciadv.aaw1317
Hanada S, Fujioka K, Inoue Y, Kanaya F, Manome Y, Yamamoto K. Cell-based in vitro blood–brain barrier model can rapidly evaluate nanoparticles’ brain permeability in association with particle size and surface modification. Int J Mol Sci 2014;15:1812-25.
DOI: https://doi.org/10.3390/ijms15021812
Kim TH, Mount CW, Gombotz WR, Pun SH. The delivery of doxorubicin to 3-D multicellular spheroids and tumors in a murine xenograft model using tumor-penetrating triblock polymeric micelles. Biomaterials 2010;31:7386-97.
DOI: https://doi.org/10.1016/j.biomaterials.2010.06.004
Goodman TT, Olive PL, Pun SH. Increased nanoparticle penetration in collagenase-treated multicellular spheroids. Int J Nanomedicine 2007;2:265-74.
Kim Y, Lobatto ME, Kawahara T, Lee Chung B, Mieszawska AJ, Sanchez-Gaytan BL, et al. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis. Proc Natl Acad Sci USA 2014;111:1078-83.
DOI: https://doi.org/10.1073/pnas.1322725111
Thomsen TB, Li L, Howard KA. Mucus barrier-triggered disassembly of SiRNA nanocarriers. Nanoscale 2014;6-12547-54.
DOI: https://doi.org/10.1039/C4NR01584C
Carvalho VFM, Migotto A, Giacone DV, de Lemos DP, Zanoni TB, Maria-Engler SS, et al. Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models. Eur J Pharm Sci 2017;109:131-43.
DOI: https://doi.org/10.1016/j.ejps.2017.07.023
Jia Z, Guo Z, Yang CT, Prestidge C, Thierry B. “Mucus-on-chip”: A new tool to study the dynamic penetration of nanoparticulate drug carriers into mucus. Int J Pharm 2021;598120391.
DOI: https://doi.org/10.1016/j.ijpharm.2021.120391
McCormick SC, Stillman N, Hockley M, Perriman AW, Hauert S. Measuring nanoparticle penetration through bio-mimetic gels. Int J Nanomedicine 2021;16:2585-95.
DOI: https://doi.org/10.2147/IJN.S292131
Kiew SF, Ho YT, Kiew LV, Kah JCY, Lee HB, Imae T, et al. Preparation and Characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability. Int J Pharm 2017;534:297-307.
DOI: https://doi.org/10.1016/j.ijpharm.2017.10.045
Ho YT, Adriani G, Beyer S, Nhan PT, Kamm RD, Kah JCY. A Facile method to probe the vascular permeability of nanoparticles in nanomedicine applications. Sci Rep 2017;7:707.
DOI: https://doi.org/10.1038/s41598-017-00750-3
Ho DN, Kohler N, Sigdel A, Kalluri R, Morgan JR, Xu C, et al. Penetration of endothelial cell coated multicellular tumor spheroids by iron oxide nanoparticles. Theranostics 2012;2:66-75.
DOI: https://doi.org/10.7150/thno.3568
Zhang M, Xu C, Jiang L, Qin J. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res (Camb) 2018; :1048-60.
DOI: https://doi.org/10.1039/C8TX00156A
Brancato V, Gioiella F, Profeta M, Imparato G, Guarnieri D, Urciuolo F, et al. 3D Tumor microtissues as an in vitro testing platform for microenvironmentally-triggered drug delivery systems. Acta Biomater 2017;57:47-58.
DOI: https://doi.org/10.1016/j.actbio.2017.05.004
Moore TL, Hauser D, Gruber T, Rothen-Rutishauser B, Lattuada M, Petri-Fink A, et al. Cellular shuttles: Monocytes/macrophages exhibit transendothelial transport of nanoparticles under physiological flow. ACS Appl Mater Interfaces 2017;9:18501-11.
DOI: https://doi.org/10.1021/acsami.7b03479
Hudecz D, Khire T, Chung HL, Adumeau L, Glavin D, Luke E, et al. Ultrathin silicon membranes for in situ optical analysis of nanoparticle translocation across a human blood–brain barrier model. ACS Nano 2020;14:1111-22.
DOI: https://doi.org/10.1021/acsnano.9b08870
Brun E, Barreau F, Veronesi G, Fayard B, Sorieul S, Chanéac C, et al. Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia. Part Fibre Toxicol 2014;11:13.
DOI: https://doi.org/10.1186/1743-8977-11-13
Brandenberger C, Rothen-Rutishauser B, Mühlfeld C, Schmid O, Ferron GA, Maier KL, et al. Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model. Toxicol Appl Pharmacol 2010;242:56–65.
DOI: https://doi.org/10.1016/j.taap.2009.09.014
Raemy DO, Limbach LK, Rothen-Rutishauser B, Grass RN, Gehr P, Birbaum K, et al. Cerium oxide nanoparticle uptake kinetics from the gas-phase into lung cells in vitro is transport limited. Eur J Pharm Biopharm 2011;77:368-75.
DOI: https://doi.org/10.1016/j.ejpb.2010.11.017
Yang Y, Yang X, Zou J, Jia C, Hu Y, Du H, et al. Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model. Lab Chip 2015,15:735-44.
DOI: https://doi.org/10.1039/C4LC01065E
Wang HF, Liu Y, Wang T, Yang G, Zeng B, Zhao CX. Tumor-microenvironment-on-a-chip for evaluating nanoparticle-loaded macrophages for drug delivery. ACS Biomater Sci Eng 2020;6:5040-50.
DOI: https://doi.org/10.1021/acsbiomaterials.0c00650
Han B, Fang WH, Zhao S, Yang Z, Hoang BX. Zinc sulfide nanoparticles improve skin regeneration. Nanomedicine 2020;29:102263.
DOI: https://doi.org/10.1016/j.nano.2020.102263
Hao F, Jin X, Liu QS, Zhou Q, Jiang G. Epidermal penetration of gold nanoparticles and its underlying mechanism based on human reconstructed 3D Episkin model. ACS Appl Mater Interfaces 2017;9:42577-88.
DOI: https://doi.org/10.1021/acsami.7b13700
Englert C, Trützschler AK, Raasch M, Bus T, Borchers P, Mosig AS, et al. Crossing the blood-brain barrier: Glutathione-conjugated poly(ethylene imine) for gene delivery. J Control Release 2016;241:1–14.
DOI: https://doi.org/10.1016/j.jconrel.2016.08.039
Küchler S, Wolf NB, Heilmann S, Weindl G, Helfmann J, Yahya MM, et al. 3D-wound healing model: Influence of Morphine and solid lipid nanoparticles. J Biotechnol 2010;148:24–30.
DOI: https://doi.org/10.1016/j.jbiotec.2010.01.001
Giacone DV, Dartora VFMC, de Matos JKR, Passos JS, Miranda DAG, de Oliveira EA, et al. Effect of Nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D Skin cancer models. Int J Biol Macromol 2020;165:1055–65.
DOI: https://doi.org/10.1016/j.ijbiomac.2020.09.167
Jun SH, Kim H, Lee H, Song JE, Park SG, Kang NG. Synthesis of retinol-loaded lipid nanocarrier via vacuum emulsification to improve topical skin delivery. Polymers (Basel) 2021;13:826.
DOI: https://doi.org/10.3390/polym13050826
Wang A, Weldrick PJ, Madden LA, Paunov VN. Biofilm-Infected human clusteroid three-dimensional coculture platform to replace animal models in testing antimicrobial nanotechnologies. ACS Appl Mater Interfaces 2021;13:22182–94.
DOI: https://doi.org/10.1021/acsami.1c02679
How to Cite
Carton, F. ., & Malatesta, M. (2022). Assessing the interactions between nanoparticles and biological barriers in vitro: a new challenge for microscopy techniques in nanomedicine. European Journal of Histochemistry, 66(4). https://doi.org/10.4081/ejh.2022.3603
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- A.M. Luciano, D. Corbani, V. Lodde, I. Tessaro, F. Franciosi, J.J. Peluso, S. Modina, Expression of progesterone receptor membrane component-1 in bovine reproductive system during estrous cycle , European Journal of Histochemistry: Vol. 55 No. 3 (2011)
- L. Wang, J. Wang, X. Zhou, J. Li, Y. Shi, Z. Han, X. Wang, S. Li, Z. Yang, R. Wang, D. Fan, Y. Han, CM2 antigen, a potential novel molecule participating in glucuronide transport on rat hepatocyte canalicular membrane , European Journal of Histochemistry: Vol. 56 No. 3 (2012)
- Manuela Monti, Basic confocal microscopy , European Journal of Histochemistry: Vol. 56 No. 1 (2012)
- Carlo Alberto Redi, Embryo culture - Methods and protocols , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- C Pellicciari, MG Bottone, AI Scovassi, TE Martin, M Biggiogera, Rearrangement of nuclear ribonucleoproteins and extrusion of nucleolus-like bodies during apoptosis induced by hypertonic stress , European Journal of Histochemistry: Vol. 44 No. 3 (2000)
- C Lanni, MG Bottone, A Bardoni, K Dyne, Proliferation characteristics and polyploidization of cultured myofibroblasts from a patient with fibroblastic rheumatism , European Journal of Histochemistry: Vol. 47 No. 3 (2003)
- E Capelli, R Nano, S Panelli, L Sciola, A Spano, S Barni, Cytoskeleton actin changes in IL-2 activated cells , European Journal of Histochemistry: Vol. 44 No. 3 (2000)
- G Diaz, M Melis, A Musinu, M Piludu, M Piras, AM Falchi, Localization of MTT formazan in lipid droplets. An alternative hypothesis about the nature of formazan granules and aggregates , European Journal of Histochemistry: Vol. 51 No. 3 (2007)
- Claudio Pigoli, Lucia Rita Gibelli, Mario Caniatti, Luca Moretti, Giuseppe Sironi, Chiara Giudice, Bleaching melanin in formalin-fixed and paraffin-embedded melanoma specimens using visible light: a pilot study , European Journal of Histochemistry: Vol. 63 No. 4 (2019)
- L. Pieri, C. Sassoli, P. Romagnoli, L. Domenici, Use of periodate-lysine-paraformaldehyde for the fixation of multiple antigens in human skin biopsies , European Journal of Histochemistry: Vol. 46 No. 4 (2002)
<< < 50 51 52 53 54 55 56 57 58 59 > >>
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
0
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
12
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
