7-Ethyl-10-hydroxy-camptothecin (SN-38), an efficient
topoisomerase inhibitor, is the
biological metabolite of
irinotecan used as the first-line
chemotherapy drug for
colon cancer. However, the hydrophobicity and instability of
SN-38 limit its further clinical application. In this study, to improve water dispersity and the anti-
tumor efficiency of
SN-38, a
prodrug, SN-38-BOC, that could efficiently transform to active
SN-38 in the acidic tumor microenvironment was synthesized and encapsulated into
MPEG-P(CL-ran-TMC)
micelles (SN-38-BOC micelles). SN-38-BOC
micelles could accumulate in
tumors due to the EPR effect and exhibit a sustained release behavior, which was rapidly transformed to active
SN-38 by the acidic environment of
tumor tissues (pH 5.5-6.8), thus achieving efficient anti-
tumor activity. Compared with the free SN-38-BOC group, enhanced cytotoxicity and apoptotic induction were obtained from the SN-38-BOC
micelle-treated group in both HCT116 and CT26 cells. In addition, SN-38-BOC
micelles showed more effective anti-angiogenesis than free SN-38-BOC in a transgenic zebrafish model. Furthermore, SN-38-BOC
micelles exhibited stronger inhibition of
tumor growth in both HCT116 and CT26 subcutaneous xenograft
tumor models. Histological analysis revealed that SN-38-BOC
micelles showed a more effective anti-
tumor activity than the free
drug by inducing more apoptosis, inhibiting angiogenesis, and suppressing proliferation. Thus, the pH-activatable SN-38-BOC
micelle could serve as a promising candidate in
colorectal tumor therapy.