Polymeric prodrug microspheres with tumor intracellular microenvironment bioreducible degradation, pH-triggered “off-on” fluorescence and drug release for precise imaging-guided diagnosis and chemotherapy

Publication date: Available online 4 February 2019Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Mingliang Pei, Guoping Li, Kangwei Ma, Jianan Li, Yuanfan Wang, Peng LiuAbstractTheranostic nanoplatforms have been recognized for imaging-guided diagnosis and chemotherapy of cancer by integrating imaging function into the drug delivery systems (DDSs). Here, a facile approach was developed for the fabrication of polymeric prodrug microspheres by introducing pH sensitive “off-on” fluorochrome Rhodamine 6 G into bioreducible cleavable bisulfide crosslinked PEGylated poly(glycidyl methacrylate) (PEG-PGMA) microspheres, followed with chemical conjugation of doxorubicin (DOX) via an acid-labile hydrazone linkage. High drug content of 25.4% was achieved for the final PEG-PGMA-Hy-DOX prodrug microspheres with average hydrodynamic diameter of 332 nm. The in vitro controlled release showed leakage-free in physiological medium but a sustained drug release up to 58% within 56 h in tumor intracellular microenvironment. The cellular experiments showed that the PEG-PGMA-Hy-DOX prodrug microspheres could be effectively internalized into HepG2 cells with enhanced anti-tumor efficacy than the free DOX. Furthermore, they showed fluorescence only in tumor intracellular microenvironment, indicating their promising potential for precise imaging-guided diagnosis and chemotherapy.Graphical Abstract

Source: Colloids and Surfaces B: Biointerfaces - February 5, 2019 Category: Biochemistry Source Type: research