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.
Subject(s)
Apoptosis , Breast Neoplasms , Cell Proliferation , Nanotubes, Carbon , PTEN Phosphohydrolase , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , Nanotubes, Carbon/chemistry , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , MCF-7 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistryABSTRACT
Cancer is designated as one of the principal causes of mortality universally. Among different types of cancer, brain cancer remains the most challenging one due to its aggressiveness, the ineffective permeation ability of drugs through the blood-brain barrier (BBB), and drug resistance. To overcome the aforementioned issues in fighting brain cancer, there is an imperative need for designing novel therapeutic approaches. Exosomes have been proposed as prospective "Trojan horse" nanocarriers of anticancer theranostics owing to their biocompatibility, increased stability, permeability, negligible immunogenicity, prolonged circulation time, and high loading capacity. This review provides a comprehensive discussion on the biological properties, physicochemical characteristics, isolation methods, biogenesis and internalization of exosomes, while it emphasizes their therapeutic and diagnostic potential as drug vehicle systems in brain cancer, highlighting recent advances in the research field. A comparison of the biological activity and therapeutic effectiveness of several exosome-encapsulated cargo including drugs and biomacromolecules underlines their great supremacy over the non-exosomal encapsulated cargo in the delivery, accumulation, and biological potency. Various studies on cell lines and animals give prominence to exosome-based nanoparticles (NPs) as a promising and alternative approach in the management of brain cancer.
