Hyaluronic acid-based ROS-responsive prodrug for cancer treatment

Abstract

To date, chemotherapy is the main weapon against the last stages of cancer. Despite indisputable advances in science and technology over the last hundreds of years, chemotherapy still has number of drawbacks and limitations. High toxicity and solubility issues of the chemotherapeutic drug in pair of low delivery efficiency leads to severe side effects and rapid clearance. Therefore, it is important to design a potent carrier for precise and effective drug delivery. Recently, Hyaluronic acid polysaccharide–based drug conjugates have gained mass of attention due to their “stealth” effect that hides the nano system from protein corona formation. Moreover, the backbone of the polymer can be modified with chemotherapeutic through microenvironment–controlled linker. In this work, Camptothecin (CPT) anticancer drug was covalently bind to a Hyaluronic acid (HA) by Thioketal ROS–responsive linker (TK) to form amphiphilic prodrug (HTC). Hyaluronic acid is well known as biocompatible and biodegradable material used in cosmetic and medical spheres, that can also play a role as a drug carrier with active targeting for CD44 glycoprotein that is overexpressed in several cancer cell types. In this study, we designed and synthesized stimuli–responsive polymer–drug conjugates for improved targeting of cancer cells which self–assemble into core/shell micelles in aqueous media. The system will safely deliver the drug due to covalent binding and target CD44 receptor. The micelles will degrade under hyaluronidase and release the drug specifically on the tumor site under high ROS level.