It is of great significance to develop biocompatible and degradable gene carriers with stimuli-enhanced gene therapy and imaging function. In this work, low-cytotoxic polycation PGEA (ethanolamine-functionalized poly(glycidyl methacrylate))-functionalized dextran-quantum dot (QD) nanohybrids (DQ-PGEA) were proposed as safe and efficient gene carriers via a facile and feasible method. The highly water-soluble dextran gives the carrier good stability, biocompatibility, and abundant modification sites, while QDs allow fluorescence (FL) imaging. Taking advantage of the pH-responsive self-destruction characteristic introduced by Schiff base linkages, DQ-PGEA nanohybrids could not only result in enhanced gene release but also contribute to the elimination of the carriers. Reduced (nondegradable) DQ-PGEA-R nanohybrids were also synthesized as counterparts to reveal the superiority of the responsive DQ-PGEA carriers. The effectiveness of the as-prepared gene delivery systems was verified adopting the antioncogene p53 in the mouse model of breast cancer. As expected, DQ-PGEA nanohybrids demonstrated a superior gene transfection performance and antitumor inhibition compared with their counterparts. Meanwhile, the gene delivery processes could be tracked in real time to visualize the therapeutic processes and realize FL imaging-guided gene therapy. The current multifunctional stimuli-responsive nanoplatforms with the self-destruction feature are intriguing candidates to achieve enhanced gene therapy for tumor treatment.
Keywords: degradable; gene therapy; pH-responsive; polysaccharide; quantum dots.