Hypobaric hypoxia exposure regulates tissue distribution of nanomedicine for enhanced cancer therapy

Abstract

Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting to determine whether they can regulate tissue distribution of nanomedicine, especially in tumor, for enhanced cancer therapy. Hypobaric hypoxia exposure improved the pharmacokinetics of paclitaxel-loaded liposomes and facilitated their distribution in the heart and liver, whereas hyperbaric oxygen exposure did not benefit and even impaired the pharmacokinetics and distribution. Particularly, both hypobaric hypoxia and hyperbaric oxygen exposure could not improve the distribution in subcutaneous tumor. Thus, we constructed orthotopic liver tumor model and discussed whether high distribution of the liposomal nanomedicine in the liver, facilitated by hypobaric hypoxia exposure, could ensure their effective accumulation in liver tumor for enhanced cancer therapy. The liposomal nanomedicine with adjuvant hypobaric hypoxia exposure significantly inhibited the growth of orthotopic liver tumor for prolonged survival time, achieved by hypobaric hypoxia-promoted accumulation at tumor sites of the liver. It might be the first example of the application of adjuvant intermittent hypobaric hypoxia exposure in treating liver cancer.