Advanced Nanotechnology for Hypoxia-Associated Antitumor Therapy
Hypoxia is a hallmark of tumor microenvironment, which promotes the proliferation, metastasis and invasion of tumors and stimulates the resistance of cancer treatments, leading to serious consequences of tumor recurrence. Many studies on nanotechnology have been conducted to improve the efficacy of cancer treatments by using hypoxia strategy. This is usually achieved by (i) activating bioreductive prodrugs in tumor hypoxic/exacerbated hypoxic microenvironment, or (ii) delivering therapeutic agents to hypoxic tumor tissue using targeting molecules. Normally, good therapeutic effect can be expected by modulating hypoxic microenviroment for tumor treatments. To achieve this, various nanotechnology strategies based on overcoming hypoxia have been exploited to alleviate tumor hypoxia and enhance therapeutic efficacy of tumor therapy, including (i) reducing oxygen consumption by inhibiting cell respiration, (ii) normalizing tumor vessels to promote blood flow in tumor, (iii) carrying exogenous oxygen into tumor, (iv) generating oxygen in situ. The strategy of in situ oxygen production is refined, and the scope of this strategy is further expanded. Finally, the inspiration of advanced nanotechnology in hypoxia-associated antitumor therapy guides the study of tumor hypoxia for clinics.