Nanotechnology-mediated photodynamic therapy: Focus on overcoming tumor hypoxia

The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within the tumor microenvironment (TME) to regulate tumor metabolism, proliferation, and promote tumor metastasis as well as angiogenesis, consequently leading to treatment failure and recurrence. In recent years, widespread attempts have been made to overcome tumor hypoxia through different methods, such as hyperbaric oxygen therapy (HBOT), hyperthermia, O₂ carriers, artificial hemoglobin, oxygen generator hydrogels, and peroxide materials. While oxygen is found to be an essential agent to improve the treatment response of photodynamic therapy (PDT) and other cancer treatment modalities, the development of hypoxia within the tumor is highly associated with PDT failure. Recently, the use of nanoparticles has been a hot topic for researchers and exploited to overcome hypoxia through Oxygen-generating hydrogels, O₂ nanocarriers, and O₂-generating nanoparticles. This review aimed to discuss the role of nanotechnology in tumor oxygenation and highlight the challenges, prospective, and recent advances in this area to improve PDT outcomes.