Nanoarchitectonics of Doxycycline-Loaded Vitamin E–D-α-Tocopheryl Polyethylene Glycol 1000 Succinate Micelles for Ovarian Cancer Stem Cell Treatment

Abstract

Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC₅₀ values were 20 μg/ml for free drug and 5 μg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.

Plain language summary

Cancer, a global leading cause of death, has a significant impact on human health. Among the various types of cancer, ovarian cancer ranks as the seventh most prevalent, posing a significant threat to women and contributing significantly to deaths in this population. Recent studies have highlighted the importance of targeting cancer stem cells to enhance the effectiveness of cancer treatments and prevent tumor relapse. Cancer stem cells are cells that can differentiate into different cell types in a tumor, driving the growth and spread of cancer. Over the past few decades, certain antibiotics, including doxycycline, have emerged as potent and selective anticancer stem cell agents by specifically targeting mitochondrial biogenesis. In line with this, the authors developed a doxycycline-loaded micelle delivery system. Micelles are spheres made of a single layer of a type of fat called phospholipids; they have been combined with drugs to increase the successful delivery and effectiveness of that drug. This research revealed that this micelle formulation demonstrated a fourfold increase in efficacy against ovarian cancer stem cells compared with free antibiotics. Moreover, it efficiently reduced colony formation and CD44 biomarker levels among the stem cells, indicating damage to cancer stem cells. These findings underscore the potential of this doxycycline-loaded micelle system as a promising approach for eradicating ovarian cancer stem cells and improving therapeutic outcomes.

Graphical abstract

Keywords::

• cancer stem cell
• doxycycline
• micelle
• ovarian cancer
• TPGS

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2022-0274

Financial disclosure

This work was supported by research affairs of Tehran University of Medical Science (TUMS) with grant no. 41156. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by research affairs of Tehran University of Medical Science (TUMS) with grant no. 41156. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.