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Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care.However,the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS.In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen,colon cancer xenograft mice (SW620 cell line) were treated by PLD,AA,or combined regimes,respectively;the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining;the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis.In addition,the impact of AA on collagen synthesis of fibroblast cell (HFL-1) and cytotoxic effect of PLD and doxorubicin to cancer cell (SW620) were studied in vitro.In the presence of AA (4 mg/kg),the intratumor collagen level was restricted in vivo (reduced by 22％,from 4.14％ ± 0.30％ to 3.24％ ± 0.25％,P =0.051) and in vitro.Subsequently,doxorubicin level was increased by ～30％.The antitumor activity of PLD was significantly improved (57.3％ inhibition of tumor growth and 44％ reduction in tumor weight) by AA combination.Additionally,no significant improvement in cytotoxic effect of PLD or doxorubicin induced by AA was observed.In conclusion,AA is a promising sensitizer for tumor treatment by enhancing intratumor drug exposure via stromal remodeling.