The combination of photothermal and
photodynamic therapy (PTT/
PDT) shows pronounced potential as a prominent therapeutic strategy for
tumor treatment. However, the efficacy is limited by insufficient
tumor-targeted delivery of PTT and
PDT reagents and the hypoxic nature of the tumor microenvironment. To overcome these limitations,
tumor acidity-responsive
lipid membrane-enclosed
perfluorooctyl bromide oil droplet nanoparticles (NPs) surface modified with N-acetyl
histidine-modified D-α-tocopheryl
polyethylene glycol 1000 succinate (
PFOB@IMHNPs) were developed, capable of co-delivering
oxygen, IR780 (a photothermal agent) and
mTHPC (a photodynamic sensitizer) into
tumors. Through self-sufficient
oxygen transportation in combination with promotion of cellular uptake upon
acid-triggered generation of surface positive charge, the
PFOB@IMHNPs effectively delivered IR780 and
mTHPC and produced
singlet oxygen within hypoxic TRAMP-C1 cells following exposure to irradiation at 660 nm. This led to effective killing of hypoxic
cancer cells in vitro. Importantly, when irradiation at 808 and 660 nm was carried out, PT/PD combination
therapy utilizing
PFOB@IMHNPs dramatically suppressed the growth of TRAMP-C1
tumors through effective
tumor-targeted cargo delivery and relief of tumor hypoxia. Our results suggest the high potential of the
PFOB@IMHNPs developed in this study in clinical application for
cancer treatment.