Transferrin-Decorated PLGA Nanoparticles Loaded with an Organoselenium Compound as an Innovative Approach to Sensitize MDR Tumor Cells: An In Vitro Study Using 2D and 3D Cell Models

• Published in: Nanomaterials (Basel, Switzerland) Vol. 13; no. 16; p. 2306
• Main Authors: Macedo, Letícia Bueno, Nogueira-Librelotto, Daniele Rubert, Mathes, Daniela, Pieta, Taís Baldissera, Mainardi Pillat, Micheli, Rosa, Raquel Mello da, Rodrigues, Oscar Endrigo Dorneles, Vinardell, Maria Pilar, Rolim, Clarice Madalena Bueno
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-08-2023; MDPI
• Subjects: 3D cell culture; Acids; active targeted drug delivery; Alpha hydroxy acids; Anticancer properties; Antitumor activity; Apoptosis; Aqueous solutions; Cancer; Cancer therapies; Cell culture; Cell cycle; Cell migration; cell uptake; Chemotherapy; Cytotoxicity; Decoration; Drug delivery; Drug delivery systems; Effectiveness; in vitro antitumor activity; Internalization; Lactic acid; Multidrug resistance; multidrug resistance (MDR); Nanoparticles; Organoselenium compounds; Polylactide-co-glycolide; Polymers; Properties; selenium compound; Spheroids; Structure; Three dimensional models; Toxicity; Transferrin; Transferrins; Tumor cell lines; Tumor cells; Tumors; Brazil; Spain; United States > US; Japan
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano13162306

Multidrug resistance (MDR) is the main challenge in cancer treatment. In this sense, we designed transferrin (Tf)-conjugated PLGA nanoparticles (NPs) containing an organoselenium compound as an alternative to enhance the efficacy of cancer therapy and sensitize MDR tumor cells. Cytotoxicity studies were performed on different sensitive tumor cell lines and on an MDR tumor cell line, and the Tf-conjugated NPs presented significantly higher antiproliferative activity than the nontargeted counterparts in all tested cell lines. Due to the promising antitumor activity of the Tf-decorated NPs, further studies were performed using the MDR cells (NCI/ADR-RES cell line) comparatively to one sensitive cell line (HeLa). The cytotoxicity of NPs was evaluated in 3D tumor spheroids and, similarly to the results achieved in the 2D assays, the Tf-conjugated NPs were more effective at reducing the spheroid’s growth. The targeted Tf-NPs were also able to inhibit tumor cell migration, presented a higher cell internalization and induced a greater number of apoptotic events in both cell lines. Therefore, these findings evidenced the advantages of Tf-decorated NPs over the nontargeted counterparts, with the Tf-conjugated NPs containing an organoselenium compound representing a promising drug delivery system to overcome MDR and enhance the efficacy of cancer therapy.