Recently, The research team of Li Zhihong, Department of Orthopedics and Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, published an online research article titled Targeting Bone Tumor and Subcellular Endoplasmic Reticulum via Near Infrared Ⅱ Fluorescent Polymer for Photodynamic-Immunotherapy to Break the Step-Reduction Delivery Dilemma in the form of Research Article on Advanced Science (IF: 17.521, a top journal in CAS Q1). Prof. Li Zhihong and Prof. Liu Tang from the the Second Xiangya Hospital of Central South University are the co-corresponding authors. Doctoral student Zhang Xianghong is the first author. The Second Xiangya Hospital of Central South University is the first affiliation.

The article first reported a cascade targeting near infrared II (NIR II) fluorescent nanoparticles(NPER/BO-PDT), which can break the Step-Reduction Delivery Dilemma(SRDD) and achieve photodynamic-immunotherapy. Multiple physiologic physical barriers of solid tumors exist including diseased organs, tissues, cells, and even subcellular organelles which results in the delivery of any drugs to the final targeted following a step-reduction manner and greatly threatens anticancer drugs to exert their efficacy.

In recent years, photodynamic therapy (PDT) is a promising anti-tumor therapy, which relies on photosensitizers (PSs) to produce light-dependent reactive oxygen species (ROS) to efficientlykill tumor cells,. However, efficient and precise transportation of PSs is still challenging, due to a SRDDwhich also threatens anticancer drug delivery to exert their efficacy. In addition, Endoplasmic reticulum (ER) is a cell organelle for protein synthesis which determines the function, fate, and survival of cells. Therefore,that PSs could be delivered to the tumor cells and then translocated to ER is of great importance.

To this end, the team developed a cascade targeting near infrared II fluorescent nanoparticles(NPER/BO-PDT). The study has shown that the nanoparticles could break SRDD in solid tumors, achieve targeted delivery of nano-drug to bone tumors and endoplasmic reticulum, induce continuous intracellular ROS generation, trigger endoplasmic reticulum stress and cause potent immune cell death(ICD), boost strong system immune response of Osteosarcoma(OS), and then effectively promote dendritic cell (DCs) maturation and enhance their antigen presentation ability, ultimately reach more effective photodynamic-immunotherapy. Prof. Li Zhihong's team has long been dedicated to the clinical integrated treatment of bone and soft tissue tumors, pathogenesis of oncogenes and cytokines in bone tumors, tumor model development and translational application research, providing a new therapeutic idea for the treatment of bone sarcoma. The team closely integrates clinical and research basic studies, builds a standardized biological sample bank to carry out more clinical studies, and realizes precise treatment for patients, which will hopefully change the existing treatment pattern of OS patients and usher in a real therapeutic breakthrough.

Link to the original article: https://onlinelibrary.wiley.com/doi/10.1002/advs.202201819