Yaoguang She,Jianxin Cui,Jiamin Ye,Fei Pan,Wenquan Liang,Xiaofeng He,Di Wu,Xiaoyuan Ji,Chunxi Wang
Peritoneal metastasis (PM) is a terminal stage of gastrointestinal cancers, often resulting in poor survival outcomes. Traditional treatments like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown some effectiveness but are associated with significant risks. This study presents a novel nanomotor-based drug delivery system (M@MnO 2 –Au-mSiO 2 @CDDP) designed to enhance the efficacy of PM treatment. By utilizing an oxygen-driven heterojunction nanomotor (MnO 2 –Au-mSiO 2 ), coated with membrane of M1-type macrophages, the system targets PM tumors with high precision through intraperitoneal perfusion. These biomimetic NMs promote deep tumor penetration, enhance reactive oxygen species (ROS) generation, and activate the STING pathway, a critical component in immune regulation. The catalytic properties of MnO 2 within the nanomotors enhance drug permeability and retention, enabling targeted and controlled drug release. Both in vitro and in vivo experiments demonstrated the system's ability to significantly inhibit tumor growth, induce apoptosis, and activate immune responses. In addition, the synergistic effect of targeted drug delivery, catalytic therapy and immunotherapy of this system was further confirmed by constructing an in vitro gastric cancer organoid model, showing great clinical application potential. The study also confirmed excellent biocompatibility and stability, making these NMs a promising clinical tool for the treatment of PM. This research underscores the potential of nanotechnology to revolutionize cancer treatment by overcoming the limitations of traditional therapies and paving the way for future innovations in targeted cancer therapies.
Given the unique anatomy and location of inflammatory bowel disease (IBD), oral pharmacological treatment is the mainstay for managing IBD because of its convenience and direct accessibility to the gastrointestinal tract. However, efficient delivery systems must be designed to navigate the harsh gastrointestinal environment during application. Here, an innovative oral drug delivery system was proposed using nanomotor (NM)-loaded soluble microcapsules for treating IBD. MnO 2 -Au-mSiO 2 NMs incorporate partially encapsulated MnO 2 antennas that convert reactive oxygen species into oxygen, autonomously propelling the NMs. Astaxanthin (AST), known for its anti-inflammatory properties, is loaded into the mesoporous silica (mSiO 2 ) of NMs (AST@NMs). AST effectively reduces inflammation and shifts macrophages from a proinflammatory (M1) phenotype to an anti-inflammatory (M2) phenotype. To protect the nanomotors from harsh digestive conditions and achieve intestinal-responsive release, using photocurable 3D printing, we fabricated enteric-coated oral microcapsules (MCs). Additionally, to prevent leakage of AST@NMs, a calcium alginate shell was cured in situ on the surface of the microcapsules (AST@NMs@MCs). In vitro and in vivo, AST@NMs@MCs effectively reduced inflammation, repaired the intestinal barrier, and modulated the gut microbiota. These findings underscore the protective effects of the microcapsules on AST@NM, highlighting their potential as a promising strategy for treating colitis.
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