Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles

Abstract

Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm², 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide-a has the potential to be used in tumor-targeted PDT.

Keywords:

• photodynamic therapy
• photosensitizer
• pyropheophorbide-a
• nanoparticle

Supplementary materials

Figure S1 Characterization of Pyro-loaded PEG-PLGA NPs after incubation in PBS for 24 hours.

Notes: (A) DLS measurement of the NPs and (B) zeta-potential of the NPs after the Pyro-loaded NPs were incubated in PBS in a water-bath shaker at 37°C for 24 hours.

Abbreviations: Pyro, pyropheophorbide-a; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic acid); NPs, nanoparticles; PBS, phosphate-buffered saline; DLS, dynamic light scattering.

Figure S2 HPLC of Pyro.

Notes: HPLC was performed using a 150×4.6 mm, C18 column, with a 0.6 mL/min flow rate at λ=680 nm. The column was initially held at 10% CH₃CN (0.14% TFA), 90% H₂O (0.14% TFA). The concentration of CH₃CN was increased to 50% in 10 minutes and then to 90% in 35 minutes; this was maintained for 5 minutes. The column was washed with 100% CH₃CN for 15 minutes and allowed to equilibrate at the initial mobile phase conditions for 15 minutes before the next injection.

Abbreviations: HPLC, high-performance liquid chromatography; Pyro, pyropheophorbide-a; TFA, trifluoroacetic acid.

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (31270926), National High Technology Research and Development Program of China (SS2014AA021601), and the Major Program of the National Natural Science Foundation of China (31527801).

Disclosure

The authors report no conflicts of interest in this work.