ABSTRACT
As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal-organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.
Subject(s)
Immunotherapy , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Mice , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Tumor Microenvironment/drug effects , High-Intensity Focused Ultrasound Ablation , Cell Line, Tumor , Mice, Inbred BALB C , Cell Proliferation/drug effects , Prodrugs/chemistry , Prodrugs/pharmacology , Female , Neoplasms/therapy , Neoplasms/diagnostic imaging , Neoplasms/pathology , Neoplasms/immunology , HypoxiaABSTRACT
Objective: To investigate the absorption and distribution of nitrogenï¼ N ), phosphorusï¼ Pï¼ and potassiumï¼ Kï¼ in Atractylodes macrocephala by field experiment. Methods: The samples of Atractylodes macrocephala were carried out in different growing periods,and the amount of dry matter and the contents of N,P and K in different parts of the plant were determined,respectively. Results: The results showed that one-year-old Atractylodes macrocephala of budding stage and rhizome swelling stage were the key period of rapid nutrient absorption, and the absorbed nutrient element mainly allocated to the aerial part. For the two-year-old Atractylodes macrocephala, flowering stage was the key period of rapid nutrient absorption, and the absorbed nutrient element mainly allocated to the rhizome. The average N,P2O5 and K2O absorption per 100 kg rhizome product in two-year-old Atractylodes macrocephala were 2. 65,0. 91 and 2. 16 kg, respectively. Conclusion: In addition to the appropriate base fertilizer, one-year-old Atractylodes macrocephala cultivation should pay attention to the topdressing during the budding stage and the rhizome swelling stage, while the two-year-old Atractylodes macrocephala cultivation should pay attention to the topdressing during the flowering stage.