Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

Multifunctional porous microspheres encapsulating oncolytic bacterial spores and their potential for cancer immunotherapy.

Clostridium novyi-NT (C. novyi-NT) is an anaerobic bacterium that can be used for targeted cancer therapy because it germinates selectively in the hypoxic regions of tumor tissues. However, systemic administration of C. novyi-NT spores cannot effectively treat tumors because of the limited intratumoral delivery of active spores. In this study, we demonstrated that multifunctional porous microspheres (MPMs) containing C. novyi-NT spores have the potential for image-guided local tumor therapy. The MPMs can be repositioned under an external magnetic field, enabling precise tumor targeting and retention. Polylactic acid-based MPMs were prepared using the oil-in-water emulsion technique and then coated with a cationic polyethyleneimine polymer prior to loading with negatively charged C. novyi-NT spores. The C. novyi-NT spores delivered by MPMs were released and germinated in a simulated tumor microenvironment, effectively secreting proteins cytotoxic to tumor cells. In addition, the germinated C. novyi-NT induced immunogenic death of the tumor cells and M1 polarization of macrophages. These results indicate that MPMs encapsulated with C. novyi-NT spores have great potential for image-guided cancer immunotherapy.

Flexible 3D Nanonetworked Silica Film as a Polymer-Free Drug-Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus.

Loading and eluting drugs on self-expandable metallic stents (SEMSs) can be challenging in terms of fabrication, mechanical stability, and therapeutic effects. In this study, a flexible 3D nanonetworked silica film (NSF) capable of withstanding mechanical stress during dynamic expansion is constructed to function as a drug delivery platform on an entire SEMS surface. Despite covering a broad curved area, the synthesized NSF is defect-free and thin enough to increase the stent strut diameter (110 µm) by only 0.4 percent (110.45 µm). The hydrophobic modification of the surface enables loading of 4.7 times the sirolimus (SRL) concentration in NSF than Cypher, polymer-coated commercial stent, which is based on the same thickness of coating layer. Furthermore, SRL-loaded NSF exhibits a twofold delay in release compared to the control group without NSF. The SRL-loaded NSF SEMS significantly suppresses stent-induced tissue hyperplasia than the control SEMS in the rat esophagus (all variables, p < 0.05). Thus, the developed NSF is a promising polymer-free drug delivery platform to efficiently treat esophageal stricture.

Silver Nanofunctionalized Stent after Radiofrequency Ablation Suppresses Tissue Hyperplasia and Bacterial Growth.

Intraductal radiofrequency (RF) ablation combined with placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction has risks such as stent- and heat-induced biliary sludge and restenosis. Here, we investigated the efficacy of a silver nanoparticles (AgNPs)-coated SEMS to inhibit tissue hyperplasia and bacterial growth caused by RF ablation with stent placement in the rabbit bile duct. The release behavior and antibacterial effects of AgNPs-coated SEMSs were evaluated. Then, SEMSs were successfully placed in all rabbits immediately after RF ablation. Ag ions were rapidly released at the beginning and then showed a gradual release behavior. The AgNPs-coated SEMS significantly inhibited bacterial activity compared to the uncoated SEMS (p < 0.05). Cholangiography and histological examination confirmed that the level of tissue hyperplasia was significantly lower in the AgNPs group than in the control group (all p < 0.05). Immunohistochemistry analyses revealed that TUNEL-, HSP 70-, and α-SMA-positive areas were significantly lower in the AgNPs group than in the control group (all p < 0.05). Intraductal RF ablation combined with nanofunctionalized stent placement represents a promising new approach for suppressing thermal damage as well as stent-induced tissue hyperplasia and bacterial growth.