The treatment of metastatic
cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in
tumor have always been our pursuit in
cancer therapy, especially to advance
cancer with
metastasis, for increasing the efficacy and biosafety. We established a smart nanosized
micelle, formed by
tocopherol succinate (TOS) conjugated
hyaluronic acid (HA) using a
disulfide bond linker. The
micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed
tumor, and response selectively to high GSH level in the cells, inducing
disulfide bond breakage and the release of the payload (
paclitaxel, PTX). To predict the antitumor efficacy of the
micelles more clinically, we established an orthotopic
colon cancer model with high
metastasis rate, which could be visualized by the
luciferase bioluminescence. Our data confirmed CD44 high expression in the
colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of
cancer cells in intestines demonstrated an exact recognition of our
micelles to orthotopic colon
tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released
Nile Red from the
micelles was found only in the
tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the
cancer cells, indicating a highly selective drug release. Our
micelles presented an excellent
therapeutic effect against metastatic
colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced
cancers with high CD44 receptor expression.