Nanotechnology-driven targeted therapies for gastrointestinal diseases: State-of-the-art strategies and future directions

Recent advances in nanotechnology have enabled transformative strategies for addressing the multifaceted challenges associated with gastrointestinal (GI) diseases. These disorders, encompassing inflammatory bowel diseases, colorectal cancer, and infections like Helicobacter pylori , often demand precise therapeutic delivery and reduced systemic toxicity—requirements that conventional treatments struggle to meet. Nanomedicine offers a paradigm shift by leveraging diverse nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, exosomes, and inorganic platforms to enhance drug solubility, protect labile drugs, and achieve controlled and site-specific delivery. This review outlines the latest passive and active targeting strategies, including ligand-mediated approaches and stimuli-responsive release systems, which improve drug accumulation at disease sites. It also highlights oral delivery challenges posed by the gastrointestinal microenvironment and discusses engineering solutions such as surface modification and protective coatings. Furthermore, plant-derived and cell-derived vesicle-like nanoparticles are emerging as bioinspired delivery vectors offering biocompatibility and immune modulation. We synthesize current preclinical and clinical progress, emphasizing nanomedicines already under investigation or approved for GI conditions. Despite promising data, barriers such as scalable production, regulatory complexities, and long-term safety concerns remain. This review concludes by charting future directions that focus on personalized therapy, biosensing integration, and intelligent nanoplatforms. By dissecting the intersection of materials science, pharmacology, and gastroenterology, this work provides a roadmap for accelerating translational breakthroughs in GI-targeted nanotherapies.