Photodynamic ablation of floating lung cancer cells using PVA and TPGS emulsified PLGA nanoparticles loaded with pyropheophorbide-a.

Metastasis or the spread of cancer cells to other tissues is a hallmark that leads to the majority of cancer-related deaths worldwide. When metastasizing cancer cells invade into the bloodstream, they become floating cells, also known as circulating tumor cells (CTCs), which can lead to the development of metastasis-associated multidrug resistance in advanced cancer patients. Eradication of CTCs has received much attention as a strategy for preventing metastasis. Photodynamic therapy (PDT) has attracted growing interest as a minimally invasive approach for cancer treatment. Pyropheophorbide-a (PPa) is photosensitizer with advantages of relatively high wavelength absorption and high extinction coefficient; however, it has limited PDT therapeutic benefits due to poor solubility. This work aimed to employ PDT for killing CTCs by utilizing PVA and TPGS coated PLGA nanoparticles, loaded with PPa. The PPa-entrapped PLGA nanoparticles (PPa-NPs) exhibited a spherical morphology under TEM with an average size of 124.9 ± 2.3 nm and a zeta potential value of -32.0 ± 1.4 mV. The PPa-NPs enhanced singlet oxygen generation in water upon light activation. PPa-NPs successfully delivered PPa into A549 floating cells under CTC-mimicking conditions, with 21-fold increase in intracellular PPa accumulation when compared to free PPa treatment. After red light excitation, intracellular ROS level was elevated in PPa-NPs treated floating cells, in a dose-dependent manner, and correlated with photocytotoxic effect of PPa-NPs in the floating cells. Our results demonstrate that PVA and TPGS stabilized PLGA NPs efficiently preserved the photophysical properties of PPa for eradicating CTCs by PDT with red light activation.