Hyaluronic acid carrier-based photodynamic therapy for head and neck squamous cell carcinoma

透明质酸载体光动力治疗头颈部鳞状细胞癌

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作者:Ti Zhang, Moustafa M Abdelaziz, Shuang Cai, Xinmai Yang, Daniel J Aires, M Laird Forrest

Conclusions

These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.

Purpose

Conventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment.

Results

PPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05). Conclusions: These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.

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