PMID- 34778661 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211117 IS - 2470-1343 (Electronic) IS - 2470-1343 (Linking) VI - 6 IP - 44 DP - 2021 Nov 9 TI - Toxicological Evaluations in Macrophages and Mice Acutely and Chronically Exposed to Halloysite Clay Nanotubes Functionalized with Polystyrene. PG - 29882-29892 LID - 10.1021/acsomega.1c04367 [doi] AB - Halloysite clay nanotubes (HNTs) have been proposed as highly biocompatible for several biomedical applications. Various polymers have been used to functionalize HNTs, but scarce information exists about polystyrene for this purpose. This work evaluated polystyrene-functionalized HNTs (FHNTs) by comparing its effects with non-FHNTs and innocuous talc powder on in vitro and in vivo models. Monocyte-derived human or murine macrophages and the RAW 264.7 cell line were treated with 0.01, 0.1, 1, and 100 mug mL(-1) FHNTs, HNTs, or talc to evaluate the cytotoxic and cytokine response. Our results show that nanoclays did not cause cytotoxic damage to macrophages. Only the 100 mug mL(-1) concentration induced slight proinflammatory cytokine production at short exposure, followed by an anti-inflammatory response that increases over time. CD1 mice treated with a single dose of 1, 2.5, or 5 mg Kg(-1) of FHNTs or HNTs by oral and inhalation routes caused aluminum accumulation in the kidneys and lungs, without bodily signs of distress or histopathological changes in any treated mice, evaluated at 48 h and 30 days post-treatment. Nanoclay administration simultaneously by four different parenteral routes (20 mg Kg(-1)) or the combination of administration routes (parenteral + oral or parenteral + inhalation; 25 mg Kg(-1)) showed accumulation on the injection site and slight surrounding inflammation 30 days post-treatment. CD1 mice chronically exposed to HNTs or FHNTs in the bedding material (ca 1 mg) throughout the parental generation and two successive inbred generations for 8 months did not cause any inflammatory process or damage to the abdominal organs and the reproductive system of the mice of any of the generations, did not affect the number of newborn mice and their survival, and did not induce congenital malformations in the offspring. FHNTs showed a slightly less effect than HNTs in all experiments, suggesting that functionalization makes them less cytotoxic. Doses of up to 25 mg Kg(-1) by different administration routes and permanent exposure to 1 mg of HNTs or FHNTs for 8 months seem safe for CD1 mice. Our in vivo and in vitro results indicate that nanoclays are highly biocompatible, supporting their possible safe use for future biomedical and general-purpose applications. CI - (c) 2021 The Authors. Published by American Chemical Society. FAU - Toledano-Magana, Yanis AU - Toledano-Magana Y AUID- ORCID: 0000-0002-2595-7939 AD - Escuela de Ciencias de la Salud, Universidad Autonoma de Baja California, Ensenada, Baja California 22890, Mexico. FAU - Flores-Santos, Leticia AU - Flores-Santos L AD - AddiCo, Av. Jesus del Monte, Ciudad de Mexico 52764, Mexico. FAU - Montes de Oca, Georgina AU - Montes de Oca G AD - CIATEQ Centro de Tecnologia Avanzada, Circuito de la Industria Pte Lte 11 Mza 3 No 11, Parque Industrial Ex Hacienda Dona Rosa, Lerma Edo de Mexico 52004, Mexico. FAU - Gonzalez-Montiel, Alfonso AU - Gonzalez-Montiel A AD - AddiCo, Av. Jesus del Monte, Ciudad de Mexico 52764, Mexico. FAU - Garcia-Ramos, Juan-Carlos AU - Garcia-Ramos JC AUID- ORCID: 0000-0001-9861-2467 AD - Escuela de Ciencias de la Salud, Universidad Autonoma de Baja California, Ensenada, Baja California 22890, Mexico. FAU - Mora, Conchi AU - Mora C AD - Immunology Unit, Department of Experimental Medicine, Faculty of Medicine, University of Lleida, Lleida 25002, Spain. AD - Institut de Recerca Biomedica Lleida (IRB-Lleida), Lleida 25002, Spain. FAU - Saavedra-Avila, Noemi-Alejandra AU - Saavedra-Avila NA AD - Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States. FAU - Gudino-Zayas, Marco AU - Gudino-Zayas M AD - Laboratorio de Bioinformatica, Unidad de Investigacion en Medicina Experimental, Facultad de Medicina, UNAM, Ciudad de Mexico 06720, Mexico. FAU - Gonzalez-Ramirez, Luisa-Carolina AU - Gonzalez-Ramirez LC AD - Grupo de Investigacion "Analisis de Muestras Biologicas y Forenses", Carrera Laboratorio Clinico, Facultad de Ciencias de la Salud, Universidad Nacional de Chimborazo, Riobamba 0601003, Ecuador. FAU - Laclette, Juan P AU - Laclette JP AD - Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Cd. Universitaria, Ciudad de Mexico 04510, Mexico. FAU - Carrero, Julio C AU - Carrero JC AUID- ORCID: 0000-0003-1055-5774 AD - Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Cd. Universitaria, Ciudad de Mexico 04510, Mexico. LA - eng PT - Journal Article DEP - 20211027 PL - United States TA - ACS Omega JT - ACS omega JID - 101691658 PMC - PMC8582073 COIS- The authors declare no competing financial interest. EDAT- 2021/11/16 06:00 MHDA- 2021/11/16 06:01 PMCR- 2021/10/27 CRDT- 2021/11/15 07:13 PHST- 2021/08/12 00:00 [received] PHST- 2021/10/14 00:00 [accepted] PHST- 2021/11/15 07:13 [entrez] PHST- 2021/11/16 06:00 [pubmed] PHST- 2021/11/16 06:01 [medline] PHST- 2021/10/27 00:00 [pmc-release] AID - 10.1021/acsomega.1c04367 [doi] PST - epublish SO - ACS Omega. 2021 Oct 27;6(44):29882-29892. doi: 10.1021/acsomega.1c04367. eCollection 2021 Nov 9.