Upconverting Nanoparticles as Nanotransducers for Photodynamic Therapy in Cancer Cells

Abstract

Background: Photodynamic therapy (PDT) involves killing of diseased cells by excitation of photosensitizer chemicals with high-energy light to produce cytotoxic oxygen species from surrounding dissolved oxygen. However, poor tissue penetration of high-energy light and hydrophobic photosensitizers limits the effectiveness to superficial pathologies. Upconversion phosphor nanoparticles convert low-energy radiation to higher-energy emissions. Aim:To create upconverting ‘nanotransducers’ to enable PDT in deep tissues. Results: Monodisperse, 50 nm PEI/NaYF₄:Yb³⁺,Er³⁺ nanoparticles producing green/red emission on near-infrared (NIR) excitation were targeted to folate receptors on human colon cancer cells and imaged with high signal-to-background ratio. It was demonstrated that these particles could be excited after deep intramuscular injection in rats. On NIR excitation, the particles, modified with zinc phthalocyanin photosensitizer, released singlet oxygen and, after targeted binding to cancer cells, resulted in significant cell destruction. Conclusion: Potential clinical use of these nanoparticles includes imaging and PDT of cancer in deep tissues.

Keywords::

• cancer
• HT29 cell line
• luminescence
• photodynamic therapy
• singlet oxygen
• upconversion
• wistar rats

Financial & competing interests disclosure

The authors would like to acknowledge the financial support from A∗STAR BMRC and National University of Singapore for this research. 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.

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

Ethical conduct of research

The author states that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgment

The authors thank Initha Appavoo for help with synthesis of the nanoparticles.

Additional information

Funding

The authors would like to acknowledge the financial support from A∗STAR BMRC and National University of Singapore for this research. 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.