The amount of dextran in PLGA nanocarriers modulates protein corona and promotes cell membrane damage

Author(s)

Antonio, Luana Corsi ; Ribovski, Lais ; Pincela Lins, Paula Maria ; Zucolotto, Valtencir

• Document type: Journal article
• Source: JOURNAL OF MATERIALS CHEMISTRY B; v. 10, n. 40, p. 13-pg., 2022-09-01.

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. (AU)

• FAPESP's process: 20/02386-7 - Nanomedicine applied to acute promyelocytic leukemia treatment via CD44 receptors of macrophages
• Grantee: Luana Corsi Antonio
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/00124-5 - Functionalization of nanomaterials for cancer therapy
• Grantee: Valtencir Zucolotto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/21869-6 - Theranostic nanomaterials coated with cell membrane for Nanomedicine applications
• Grantee: Paula Maria Pincela Lins
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 09/54216-9 - Acquisition of a 200kV transmission electron microscope for the characterization of nanostructures and biological materials
• Grantee: Edson Antonio Ticianelli
• Support Opportunities: Multi-user Equipment Program