Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity.Here we report a dendronized polymer-doxorubicin (DOX) hybrid (DPDH) with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate (LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4.DPDH efficiently enters 4T1 cells and releases DOX to induce cytotoxicity and apoptosis.Owing to the dendronzied structure,DPDH has a significantly longer blood circulation time than LPDC.DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological analysis.Biosafety of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological analysis.This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.