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

Affiliation

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People's Republic of China. Electronic address: [Email]

Abstract

Theranostic 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 6G 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.

Keywords

Leakage-free,Polymeric prodrug microspheres,Precise imaging-guided diagnosis and chemotherapy,pH-triggered drug release,pH-triggered fluorescence,

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