Efficiently improving solid tumor therapy through shrinking the extracellular matrix and promoting drug transport in tumor tissue via simple and known functional materials

Abstract

An effective chemotherapy through promoting drug transport in solid tumor is our concern here to avoid surgery and its side effects to our bodies. A drug delivery system, TXT-MNT-hydrogel, is constructed using temperature sensitive hydrogel nanoparticles and hydroxypropyl-β-cyclodextrin (HP-β-CD) to codeliver mannitol (MNT) and taxotere (TXT). TXT-MNT-hydrogel realizes weight inhibition in mice subcutaneous breast tumor for more 94% and 58% than TXT and a clinical used liposomes paclitaxel (Lipusu), and for more 91.4% and 85% than TXT-MNT and TXT-hydrogel as well. The mechanism is disclosed as (1) controlled taxotere and mannitol release from hydrogel nanoparticles and hydroxypropyl-β-cyclodextrin; (2) MNT shrinks the extracellular matrix of tumor tissue, and enhances the transport and bioavailability of drug in vivo for up to 2.7-fold versus no MNT in tumor surface, and from none to 0.5-2.5-fold versus the tumor surface of no MNT in the middle of tumor tissue in 12 hours, which results severer apoptosis in interior tumor cells than all the counterparts. This study certifies in vivo that the simple and published materials of MNT, TXT, HPβ-CD, and hydrogel in combination functionally augment solid tumor therapy, which provides a reference to construct more efficient drug delivery systems.