eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2025-12-30 22 4 1512 1528 10.13005/bbra/3457 56996 article Rakesh Dhole 1 Mahesh Pawar 1 Bhagyashri Ahirrao 1 Gurmeet Singh Chhabra 2 Praneeth Ivan Joel FNU 3 Nalla Seshadri 4 Department of Pharmaceutical Chemistry, KVPS’s Maharani Ahilyabai Holkar College of Pharmacy, Shirpur, India. Department of Pharmaceutical Chemistry, Indore institute of pharmacy, Pithampur road, Indore, India. Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, USA. Department of Chemistry, Lamar University, Beaumont, Texas, USA. Exemplify Biopharma Inc. East Windsor, New Jersey Tumor hypoxia, characterized by insufficient oxygen supply within the tumor microenvironment TME plays a key role in helping tumors grow, avoiding the body's immune system, and becoming resistant to treatments like chemotherapy, photodynamic therapy, and radiation. High levels of certain metabolites that are made without oxygen, such as adenosine and lactate, weaken the ability of cytotoxic T lymphocytes (CTLs) to attack cancer cells. These metabolites also reduce the production of interferon-gamma (IFN-γ) and create an environment that supports immune-suppressing cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Nanoparticle-based strategies have emerged as promising tools to alleviate hypoxia through various mechanisms, including catalytic oxygen generation, direct oxygen delivery, and targeted modulation of hypoxia-driven pathways. By enhancing oxygen availability and normalizing the aberrant TME, these nanoplatforms provide a promising avenue to overcome hypoxia-induced therapeutic resistance. This review summarizes recent progress in nanoparticle-mediated hypoxia modulation in the TME and highlights perspectives for future clinical translation in cancer immunotherapy and combined treatment approaches. https://www.biotech-asia.org/vol22no4/a-review-nanoparticle-mediated-modulation-of-tumor-hypoxia-enhancing-cancer-immunotherapy-and-therapeutic-efficacy/ Tumor hypoxia; Tumor microenvironment; Nanoparticles; Oxygen delivery; immunosuppression; Cytotoxic T lymphocytes; Photodynamic therapy; Radiotherapy; therapeutic resistance; Nanomedicine