Self-Assembled Hybrid Nanogel as a Multifunctional Theranostic Probe for Enzyme-Regulated Ultrasound Imaging and Tumor Therapy

Abstract

Multifunctional theranostic nanoprobes integrated with stimuli-responsive imaging and therapeutic capabilities have shown great potential to enhance the early cancer diagnostic efficacy and therapeutic efficiency. Elevated levels of lactate and hydrogen peroxide have been considered as the characteristic feature of the tumor microenvironment and can thus be exploited for developing promising theranostic strategies. We demonstrate here that the biocompatible and responsive enzyme-based nanogel probe has been designed as a promising theranostic tool to target high lactate and hydrogen peroxide for ultrasound imaging (US) and cancer treatment. We encapsulate the dual enzyme lactate oxidase (LOD) and catalase (CAT) into the self-assembled nanogels to fabricate responsive nanoprobe LOD/CAT-loaded nanogels (LCNGs). The nanoprobes can respond to the lactate and H₂O₂ rich tumor microenvironment to generate abundant oxygen, which further accumulates into microbubbles for enhanced US imaging. Besides, LCNGs@DOX has been further created by integrating the nanoprobes with doxorubicin (DOX) for cancer therapy. Both in vitro and in vivo results demonstrate enhanced US imaging and effective cell proliferation inhibition of LCNGs@DOX, allowing the preparation of safe and efficient theranostic nanoprobes capable of responsive US imaging and treating tumors.

Keywords: enzymes; nanogels; self-assembly; tumor therapy; ultrasound imaging.