Synthesis of a smart pH sensitive micelle containing hyaluronic acid-curcumin bioconjugate against colorectal cancer

Abstract

In the current study, we fabricated a pH-sensitive self-assembled CD44-targeted therapeutic micelle, comprising curcumin (CUR)-hyaluronic acid (HA) conjugate. At the first stage, the biopolymer, HA, as a back bone was attached to ethylene glycol vinyl ether (equivalent to 50% of the carboxylic acids of HA) and then hydroxyl of curcumin was attached to this linker to form a pH-responsive acetal linkage. The prepared HA-CUR conjugate was self-assembled and formed a micellar structure with size of 84 nm. The release of CUR from the prepared platform illustrated a controlled, sustained release at pH 7.4 while it was significantly accelerated at pH 5.4. The cytotoxicity and cellular uptake of the platform were evaluated against C26 as a CD44 positive and CHO as CD44 negative cells. The cytotoxicity and cellular uptake study showed higher internalization and cellular toxicity of the synthesized platform in C26 cells compared with CHO cells. In vivo study demonstrated desirable therapeutic efficacy of HA-CUR toward C26 tumor growth suppression and survival rate of BALB/c mice. These findings suggested HA-CUR as a hopeful natural product-based nanomedicine for active targeting and delivery of CUR to colon adenocarcinoma.