Phosphazene-based hybrid polyprodrug nanoparticles by incorporating carbon quantum dots for improved pH responsive fluorescence imaging-guided antitumor drug release

Multifunctional nanoparticles with the incorporation of accurate diagnosis and effective therapy have been extensively explored in tumor chemotherapy to ameliorate antitumor efficacy. Herein, an effective strategy was proposed to synthesize the fluorescent traceable and biodegradable hybrid polyprodrug nanoparticles for effective tumor intracellular microenvironment (TME)-responsive fluorescence imaging-guided antitumor drug delivery, by facile polycondensation of carbon quantum dots (CQDs) as fluorescence imaging agent, hydrazine-modified doxorubicin (DOXhyz) as a pH-responsive prodrug, and hexachlorocyclotriphosphazene (HCCP). The proposed HCCP-CQDs-DOXhyz hybrid polyprodrug nanoparticles possessed a high drug content of 62.9% and a suitable hydrodynamic diameter of 183.9 nm, which were demonstrated to be stable in normal physiological media with quenched fluorescence while hydrolyzable in TME with recovered fluorescence and cumulative drug release ratio of 75.9% within 24 h. The theranostic function of the proposed HCCP-CQDs-DOXhyz polyprodrug nanoparticles was revealed by the in vitro cellular experiments, showing enhanced inhibition of cancer cell proliferation.