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

Area of Science:

• Biochemistry
• Molecular Biology
• Nanotechnology

Background:

• Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a critical tumor suppressor protein frequently altered in cancers.
• Protein therapeutics offer significant potential but require effective delivery systems.
• Breast cancer remains a leading cause of mortality, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the tumor suppressive activity of full-length and truncated recombinant human PTEN delivered by multiwalled carbon nanotubes (MW-CNTs) in breast cancer cells.
• To investigate the role of different PTEN domains in its anti-cancer effects.
• To assess the potential of MW-CNTs as a delivery vehicle for PTEN protein therapy.

Main Methods:

• Recombinant full-length and truncated PTEN variants were cloned, overexpressed, and purified from *E. coli*.
• PTEN variants were successfully bound to MW-CNTs.
• Breast cancer cell lines (T-47D, ZR-75-1, MCF-7) were incubated with protein-functionalized MW-CNTs, and effects on cell growth and apoptosis were analyzed.

Main Results:

• Full-length PTEN-MW-CNTs significantly inhibited cancer cell proliferation and induced apoptosis in ZR-75-1 and MCF-7 cells.
• Truncated PTEN fragments demonstrated a lesser inhibitory effect compared to full-length PTEN.
• The N-terminal fragment's reduced efficacy underscored the importance of the C2 domain for full PTEN activity.

Conclusions:

• Full-length PTEN, delivered via MW-CNTs, is effective in inhibiting breast cancer growth and promoting apoptosis by modulating key apoptotic markers.
• MW-CNTs serve as a promising delivery system for PTEN protein therapy.
• These findings support further investigation in in vivo models and clinical studies for breast cancer treatment.