Versatile Polymeric Microspheres with Tumor Microenvironment Bioreducible Degradation, pH-Activated Surface Charge Reversal, pH-Triggered 'off-on' Fluorescence and Drug Release as Theranostic Nanoplatforms

摘要

Facile approach has been developed for the versatile polymeric microspheres with tumor-microenvironment bioreducible degradation, pH-activated surface charge-reversal, pH-triggered "off-on" fluorescence and drug release via emulsion copolymerization of glycidyl methacrylate (GMA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), N-rhodamine 6G-ethyl-acrylamide (Rh6GEAm) with N,N-bis(acyloyl)cystamine) (BACy) as disulfide crosslinker and functionalization. The final PGMA-DMMA microspheres showed excellent cytocompatibility, pH-triggered surface charge reversal at pH 5-6, strong fluorescence only in acidic media, and bioreducible degradation with high reductant level, indicating their promising application as theranostic nanoplatforms for precise imaging-guided diagnosis and chemotherapy. The DOX-loaded PGMA-DMMA microspheres with a drug-loading capacity of 18% and particle size of about 150 nm possessed unique pH/reduction dual-responsive controlled release, with a cumulative DOX release of 60.5% within 54 h at the simulated tumor microenvironment but a premature leakage of 8.0% under the simulated physiological condition. Enhanced inhibition efficacy against HepG2 cells was achieved than the free DOX.