CD44-Targeting Oxygen Self-Sufficient Nanoparticles for Enhanced Photodynamic Therapy Against Malignant Melanoma

Xiaoyang Hou,^1,* Yingkai Tao,^1,* Xinxin Li,^1,* Yanyu Pang,¹ Chunsheng Yang,² Guan Jiang,¹ Yanqun Liu<sup>1

1</sup>Department of Dermatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People’s Republic of China; ²Department of Dermatology, The Affiliated Huai’an Hospital of Xuzhou Medical University, The Second People’s Hospital of Huai’an, Huai’an 223002, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Guan Jiang; Yanqun Liu
Department of Dermatology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huai Hai Road, Xuzhou, Jiangsu 221002, People’s Republic of China
Email dr.guanjiang@xzhmu.edu.cn; xyfylyq@sohu.com

Objective: Nanotechnology-based photodynamic therapy (PDT) is a relatively new anti-tumor strategy. However, its efficacy is limited by the hypoxic state in the tumor microenvironment. In the present study, a poly(lactic-co-glycolic acid) (PLGA) nanoparticle that encapsulated both IR820 and catalase (CAT) was developed to enhance anti-tumor therapy.
Materials and Methods: HA-PLGA-CAT-IR820 nanoparticles (HCINPs) were fabricated via a double emulsion solvent evaporation method. Dynamic light scattering (DLS), transmission electron microscopy (TEM), laser scanning confocal microscopy, and an ultraviolet spectrophotometer were used to identify and characterize the nanoparticles. The stability of the nanoparticle was investigated by DLS via monitoring the sizes and polydispersity indexes (PDIs) in water, PBS, DMEM, and DMEM+10%FBS. Oxygen generation measurement was carried out via visualizing the oxygen bubbles with ultrasound imaging system and an optical microscope. Inverted fluorescence microscopy and flow cytometry were used to measure the uptake and targeting effect of the fluorescent-labeled nanoparticles. The live-dead method and tumor-bearing mouse models were applied to study the HCINP-induced enhanced PDT effect.
Results: The results showed that the HCINPs could selectively target melanoma cells with high expression of CD44, and generated oxygen by catalyzing H₂O₂, which increased the amount of singlet oxygen, ultimately inhibiting tumor growth significantly.
Conclusion: The present study presents a novel nanoplatform for melanoma treatment.

Keywords: catalase, hyaluronic acid, IR820, photodynamic therapy, tumor hypoxia