Zinc Phthalocyanine-Loaded Upconversion Nanoparticles for Near-Infrared-Triggered Singlet Oxygen Generation and Cancer Photodynamic Therapy

1． Introduction
Photodynamic therapy (PDT) is a minimally invasive cancer treatment wherein light-activated photosensitizers generate singlet oxygen to induce cytotoxicity. However, the limited tissue penetration of visible light restricts conventional PDT to superficial tumors. Although near-infrared (NIR) light offers deeper penetration, its photon energy is insufficient for direct photosensitizer excitation. Upconversion nanoparticles (UCNPs), capable of converting NIR into higher-energy visible light, hold great promise as a strategy to overcome this limitation.

2． Methods
NaYF4:Yb,Tm UCNP cores were encapsulated within a dual layer silica shell, followed by loading with zinc phthalocyanine as a photosensitizer. The resulting photosensitizer loaded UCNPs were evaluated for singlet oxygen generation and photocytotoxicity in HeLa and MCF 7 cells. In addition, cellular uptake assays were conducted to gain insight into their mechanism of action.

3． Results
Upon NIR irradiation, singlet oxygen generation was clearly enhanced by the UCNPs. A noticeable decline in cell viability was observed in both cell lines, with MCF 7 cells showing the greatest sensitivity, exhibiting an approximately 40% reduction at 25 μg/mL. Additionally, intracellular fluorescence from the UCNPs remained minimal across all tested concentrations, making the extent of cellular uptake difficult to determine.

4． Conclusions
These findings indicate that the synthesized photosensitizer‑loaded UCNPs exhibit NIR‑activated singlet oxygen generation and induce photocytotoxicity in HeLa and MCF‑7 cells. Nonetheless, their intracellular uptake could not be clearly confirmed under the present conditions.