anti hypoxia cancer nanodrug (ahcn) has great potential in improving the efficiency of oxygen dependent treatment of malignant tumors. However most of the studies on ahcn focus on optimizing the structure function of nanomaterials subjectively believe that nanodrugs can successfully enter the tumor be internalized play a role by enhancing the permeability retention (EPR) effect. From this traditional point of view the main obstacle ahcn needs to overcome is to cross the tumor cell membrane. However this simplistic view ignores the fact that real tumors have many physiological barriers. These barriers also prevent advanced ahcn from reaching the target tumor cells. With the development of tumor microenvironment research some researches have begun to overcome the layers of physiological barriers to enhance the tumor permeability of nanodrugs to alleviate tumor hypoxia.
the David Leong research group of National University of Singapore systematically discussed summarized the improvement of ahcn accumulation in tumor related limitations. The related review papers are published in small（ DOI:10.1002/smll.202003000 ）It’s on. In this paper the author first introduces the limitations of traditional ahcn delivery thinking points out the deficiencies of EPR effect in many tumor models as well as the obstacles that ahcn may encounter in delivering to tumor cells. Then we summarize the methods to overcome these main obstacles improve the adhesion uptake intracellular retention of ahcn. They include: reconsidering the design of physical chemical parameters of ahcn to overcome the clearance in vivo during the delivery process; when the EPR effect is insufficient using indirect targeting to supplement the deficiency of lig targeting; using ahcn to overcome the barrier normalization of vascular endothelial pericytes In order to improve the tumor permeability of ahcn tumor vascular system loose tumor matrix were used to improve the tumor permeability of ahcn; the strategy of changing the size of tumor microenvironment responsive ahcn was used to overcome the obstruction of narrow cell space; the contact area contact potential between ahcn cancer cell membrane were improved to improve the adhesion ability uptake efficiency of cancer cells; the tumor cell aggregation ability of ahcn was improved to reduce efflux. At the same time the author also summarizes the examples of using these methods to alleviate tumor hypoxia carry out oxygen dependent therapy.
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