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Title: | The amount of dextran in PLGA nanocarriers modulates protein corona and promotes cell membrane damage | Authors: | Antonio, Luana Corsi Ribovski, Lais PINCELA LINS, Paula Zucolotto, Valtencir |
Issue Date: | 2022 | Publisher: | ROYAL SOC CHEMISTRY | Source: | Journal of Materials Chemistry B, | Status: | Early view | Abstract: | Polymeric nanocarriers (NCs) are efficient vehicles to prevent drug unspecific biodistribution and increase the drug amounts delivered to tumor tissues. However, some toxicological aspects of NCs still lack a comprehensive assessment, such as their effects on cellular processes that lead to toxicity. We evaluate the interaction of poly(lactic-co-glycolic acid) (PLGA) NCs prepared using dextran (Dex) and Pluronic (R)-F127 as stabilizing agents with myocardial cells (H9C2), breast adenocarcinoma cells (MCF-7) and macrophages (RAW 264.7) to address the effect of Dex in PLGA NC formulations. By an emulsion diffusion method, doxorubicin-loaded NCs were prepared with no Dex (PLGA-DOX), 1% (w/v) Dex (Dex1/PLGA-DOX) and 5% (w/v) Dex (Dex5/PLGA-DOX). Uptake analyses revealed a significant reduction in Dex5/PLGA-DOX NC uptake by H9C2 and MCF-7, as in the case of Dex1/PLGA-DOX NCs in the absence of in vitro protein corona, revealing an effect of dextran concentration on the formation of protein corona. RAW 264.7 cells presented a greater uptake of Dex5/PLGA-DOX NCs than the other NCs likely because of receptor mediated endocytosis, since C-type lectins like SIGN-R1, mannose receptors and scavenger receptor type 1 that are expressed in RAW 264.7 can mediate Dex uptake. Despite the lower uptake, Dex5/PLGA-DOX NCs promote the generation of reactive oxygen species and oxidative membrane damage in MCF-7 and H9C2 even though cellular metabolic activity assessed by MTT was comparable among all the NCs. Our results highlight the importance of an in-depth investigation of the NC-cell interaction considering additional mechanisms of damage apart from metabolic variations, as nanoparticle-induced damage is not limited to imbalance in metabolic processes, but also associated with other mechanisms, e.g., membrane and DNA damage. | Notes: | Ribovski, L (corresponding author), Univ Sao Paulo, Phys Inst Sao Carlos, Nanomed & Nanotoxicol Grp, CP 369, BR-13566590 Sao Carlos, SP, Brazil.; Ribovski, L (corresponding author), Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands. l.ribovski@umcg.nl |
Document URI: | http://hdl.handle.net/1942/38742 | ISSN: | 2050-750X | e-ISSN: | 2050-7518 | DOI: | 10.1039/d2tb01296k | ISI #: | 000859238600001 | Rights: | The Royal Society of Chemistry 2022. Open access | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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The amount of dextran in PLGA nanocarriers modulates protein corona and promotes cell membrane damage.pdf | Early view | 3.05 MB | Adobe PDF | View/Open |
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