A Smart Theranostic Prodrug System Activated by Reactive Oxygen Species for Regional Chemotherapy of Metastatic Cancer

Abstract

Metastatic cancer is difficult to cure because of its uncontrollable nature and side effects during treatment. We constructed a reactive oxygen species (ROS)-activated smart theranostic prodrug system based on an ROS active site linked with both a targeting group and an anticancer drug for efficient regional chemotherapy of metastatic cancers. The optimized prodrug (Bio-( 8)-MB-CPT) with biotin as the targeting group displayed high sensitivity towards ROS and selectively targeting ability towards cervical cancer cells, showing highly efficient drug release (up to 92 %) in vitro. Bio-(8)-MB-CPT thus exerted strong toxicity towards cervical cancer cells, but unlike the parent drug (camptothecin),showed no toxicity towards normal cells. Moreover, the prodrug displayed significantly enhanced antitumor efficacy in vivo and eradicated the tumor with no obvious side effects (inhibition of the tumor reached up to 99.9 %).

Smart Nanoparticles for Breast Cancer Treatment Based on the Tumor Microenvironment

“…Under normal physiological conditions, ROS can be effectively neutralized by the enzymes superoxide dismutase, catalase, glutathione, and thioredoxin to control the equilibrium oxidation-reduction (redox) state. However, when redox homeostasis is destroyed or relieved, changes in ROS levels will lead to physiological and pathological changes (61,62). In addition, ROS play a positive role in regulating intracellular signal transduction pathways, with numerous biological conduits being constrained by a variety of ROS species, which are the key to maintaining cellular homeostasis.…”

An excipient-free “sugar-coated bullet” for the targeted treatment of orthotopic hepatocellular carcinoma

“…Removal of LMB by ROS activated a cascade reaction on BHA, and the active payloads on two hydroxyl groups were ultimately released. [42][43][44][45] Furthermore, LMB could be rapidly transformed to MB, which exhibited near-infrared (NIR) fluorescence emission (Fig. 1B).…”

Hypochlorous acid triggered fluorescent probes forin situimaging of a psoriasis model

“…[47][48][49] We further constructed theranostic platforms which could be activated by HOCl for drug release. [50][51][52] Using our reported response mechanism, 50 herein, a representative oxazine dye, Oxazine 1, was selected as the fluorophore. Two HOCl fluorescent probes with different functional groups were designed and synthesized (Scheme 1).…”