Scheme 1.

The scheme shows the synthesis of drug loading material DHP and the rational design of the pH and enzyme dual-sensitive hyaluronic acid-coated nanoparticles for the co-delivery of DOX and pEGFP. When arriving at the tumor tissue, HDDN is disassembled by Hyal2 in the tumor microenvironment and internalized through CD44-mediated endocytosis. In the lysosome, HDDN are further degraded by Hyal1 and other enzymes to expose the DDN. Because of the acidic condition in the lysosome, hydrazone bonds are broken and DHP releases DOX. With the sponge effect of PEI, DOX and gene escape from the lysosome and carry out the antitumor effect.

Abbreviations: DDN, DHP/DNA nanoparticles; DHP, doxorubicin-4-hydrazinobenzoic acid-polyethyleneimine conjugate; DOX, doxorubicin; HA, hyaluronic acid; HBA, hydrazinobenzoic acid; HDDN, hyaluronic acid-shielded nanoparticles; PEI, polyethyleneimine.