pH-Sensitive Porphyrin Metal-Organic Frameworks for Controlled Delivery of Para-Toluenesulfonamide and Photodynamic Cancer Therapy

Wei Zhou,1 Fan Feng,2 Jieli Zhang,3 Shuang Cao,4 Yunzhi Zhou,3 Yanming Li1 1Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 2Clinical Laboratory, The Fifth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100039, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Emergency General Hospital, Beijing, 100028, People’s Republic of China; 4School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, People’s Republic of ChinaCorrespondence: Yanming Li, Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China, Email [email protected] Yunzhi Zhou, Department of Respiratory and Critical Care Medicine, Emergency General Hospital, Beijing, 100028, People’s Republic of China, Email [email protected]: Photodynamic therapy (PDT) is a promising approach for tumor treatment. PDT for treating lung squamous cell carcinoma (LSCC) under the guidance of bronchoscopy has great potential for development. However, the use of high-intensity lasers in treatment may pose a risk of tissue damage. To address this issue, enhancing the sensitivity of tumor tissue to phototherapy is highly valuable.Methods: In this study, a simple method was employed to prepare porphyrin-metal framework nanoparticles (NPs), referred to as HA-PTS@PCN. The design of these NPs is based on the concept of tumor sensitization, constructed with the porphyrin-based metal-organic framework compound PCN-224 to load the drug para-toluenesulfonamide (PTS).Results: Multiple experiments have demonstrated that these NPs can be effectively absorbed and selectively release PTS within the acidic tumor microenvironment. Under 660 nm laser irradiation, the material releases reactive oxygen species, demonstrating effective photodynamic therapeutic effects. Additionally, due to the tumor-sensitizing properties of PTS, the treatment efficacy of these NPs on LSCC is significantly greater than that of PCN-224 alone. Both in vitro and in vivo studies confirmed that combining tumor sensitization strategies with PDT therapy for LSCC significantly enhances anticancer effects.Discussion: This study provides a universal strategy for preparing drug-loaded PDT nanoplatforms and offers a new approach for developing nanomedicine with tumor-sensitizing effects. Keywords: PTS, metal-organic framework, tumor sensitization, nanomedicine, PDT