Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells

Author:

Papi Rigini M.1ORCID,Tasioulis Konstantinos S.1ORCID,Kechagioglou Petros V.1ORCID,Papaioannou Maria A.2ORCID,Andriotis Eleftherios G.3ORCID,Kyriakidis Dimitrios A.1

Affiliation:

1. Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece

2. Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece

3. Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece

Abstract

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from E. coli, followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies.

Funder

project “PlantUP”

Operational Programme “Competitiveness, Entrepreneurship and Innovation”

Greece and the European Union

project “FILELIA-Development of edible olives friendly to a salt-reduced diet”

European Regional Development Fund and Greece

Publisher

MDPI AG

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