Rationally constructing the theranostics hydrogels for targeted CT imaging and healing of inflammatory bowel disease

Abstract

Negatively charged materials designed to adhere to the inflammatory bowel disease (IBD) lesions via electrostatic interactions are considered as classical approach for IBD diagnosis and therapy. However, the strict acidic environment of the stomach represents a major obstacle faced by oral drug delivery. Besides, the high absorption efficiency of the normal gastrointestinal (GI) tract leads to the off-target uptake of drugs, increasing the risk of systemic exposure. Herein, we developed poly (acrylic acid) (PAA)-modified CeO₂ nanoparticles (CeO₂@PAA) loaded alginate hydrogels, namely, the Alg-CeO₂@PAA, for cascade-targeted imaging and treatment of the IBD. The alginate hydrogels (Gel) could protect the CeO₂@PAA from decomposition in the acidic environment in the stomach; the CeO₂@PAA would be targeted delivered and gradually released in the intestine, and then adhered to the IBD lesions by electrostatic interactions, thus minimizing the systemic exposure of CeO₂ NPs in the normal GI tract, resulting in a 3-4-fold reduction in Ce deposition in main organs. CeO₂ NPs were capable of CT/X ray attenuation, free radicals scavenging, and immune system modulation, making them suitable for CT imaging and IBD treatment. Utilizing Alg-CeO₂ @PAA, we achieved enhanced CT imaging contrast of IBD lesions and improved therapeutic efficacy, demonstrated by reduced oxidative stress and attenuated inflammatory responses, compared to alginate hydrogels loaded with cetyltrimethylammonium bromide-modified CeO₂ (Alg-CeO₂ @CTAB) or unmodified CeO₂ (Alg-CeO₂). Overall, this work poses a different perspective for IBD lesion-specific theranostics agent design and development.