Reduction-responsive and tumor-targeted polyprodrug nanocarriers for targeting therapy of hepatocellular carcinoma

Abstract

Nanotechnology in cancer therapy increases medication bioavailability and lowers systemic toxicity. Additionally, polyprodrug delivery systems provide higher drug-carrying capacity and biosafety than traditional nano-drug delivery techniques. Nevertheless, the majority of prodrug delivery systems have low drug delivery efficiency and lack drug carriers that are targeted to the tumor environment. To address these issues, we synthesized poly(ferulic acid) (PFA) by polycondensation of ferulic acid (FA) and combined it with hyaluronic acid (HA) via disulfide bonds to create an HA-SS-PFA amphiphilic polyprodrug nano platform with redox sensitivity and targeting, which has high drug loading and good biocompatibility. Through the specific binding of HA to the CD44 receptor overexpressed in tumor cells, this polyprodrug carrier achieves the ability to deliver drugs in a precisely targeted manner, enabling rapid and selective drug release at the target site while reducing the toxicity of the drug to non-target organs. Furthermore, it is able to react favorably with the glutathione (GSH) concentration in tumor cells by employing redox-sensitive chemical bridging based on “sulfur bonding”. This causes the disulfide bond to break and the drug to be released from the carrier rapidly, ultimately leading to tumor cell apoptosis. In vivo and in vitro experiments showed that this polyprodrug nano-delivery platform could effectively inhibit hepatocellular carcinoma cells with a high tumor inhibition rate, boost the therapeutic effect of the antitumor drug and improve the therapeutic efficiency, and is a potentially efficient drug delivery strategy.