In recent decades, significant progress has been made in the development of different hypoxia-activated prodrugs (HAPs). Despite this, the use of HAPs for cancer therapy continues to face obstacles such as suboptimal therapeutic results due to challenges in accessing the hypoxic area and the development of metastases due to hypoxia. Now, researchers have suggested a novel treatment approach that can enhance HAP-based chemotherapy and inhibit tumor metastasis.

In solid tumors, hypoxic areas with low oxygen levels are commonly found close to necrotic regions. These hypoxic zones are resistant to radiotherapy and chemotherapy, making them a target for selective therapy like HAPs. However, HAPs are ineffective in reaching hypoxic regions that are distant from the blood vessel network, leading to suboptimal exposure to HAPs and consequently low efficacy chemotherapy. A team of researchers at the Chinese Academy of Sciences (CAS, Beijing, China) has created a novel hypoxia-inducible chitosan polymer that can be combined with antiangiogenic Pazopanib to form an injectable hydrogel that is sensitive to oxygen.

The enzyme-mediated chemical reactions facilitate polymer reactions to oxygen, resulting in gelation. By utilizing this oxygen-depleting hydrogel in combination with HAPs, it is possible to enhance the hypoxic environment of tumors, which can lead to increased toxicity of HAPs for targeted chemotherapy. Additionally, when the hydrogel is exposed to high levels of ROS in tumor areas, responsive linkages within the hydrogel are broken, which leads to sustained release of Pazopanib and the inhibition of pulmonary metastasis.

“This novel hydrogel can significantly remodel tumor hypoxic microenvironment as a kind of engineered niche,” said Professor Shaoli Song, a co-supervisor the study. “We hope that our results will encourage scientists to continue investigating the use of HAP-based chemotherapy to combat cancer.” 

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