Journal Article

Targeting Bone Tumor and Subcellular Endoplasmic Reticulum via Near Infrared II Fluorescent Polymer for Photodynamic‐Immunotherapy to Break the Step‐Reduction Delivery Dilemma

Li, Zhihong, Mo, Fuhao, Jia, Jinpeng, Liu, Tang, Wan, Jia, Xiao, Haihua, Tang, Dongsheng, Zhang, Xianghong

2022

Overview

Specific localization of photosensitizers (PSs) to a certain organelle could result in targeted attack to cause greater trauma to cancer cells, eventually maximizing photodynamic therapy (PDT). However, currently, efficient and precise transportation of PSs via drug delivery to tumor cells and subcellular organelles is still challenging, due to a so‐called step‐reduction delivery dilemma (SRDD) which also threatens anticancer drug delivery to exert their efficacy. Herein, a cascade targeting near infrared II (NIR II) fluorescent nanoparticles (NPER/BO‐PDT) is designed that can target bone tumor first and then target the subcellular organelle of endoplasmic reticulum (ER). It is found that NPER/BO‐PDT achieves the targeted accumulation of the bone tumor and then ER. NPER/BO‐PDT generates reactive oxygen species (ROS) in the subcellular organelles of ER under near infrared light irradiation. The continuous ER stress by ROS promotes the release of more damage‐associated molecular patterns, induces immunogenic cell death, stimulates the adaptive immune response, and further synergistically inhibits tumor growth, achieving the so‐called photodynamic‐immunotherapy. Overall, this study exemplifies a safe and efficient nano‐drug delivery system for a bone and ER cascade targeting via delivery of PSs to break the SRDD and highlights potential clinical translation. To break the step‐reduction delivery dilemma (SRDD), near infrared II fluorescent cascade targeting nanoparticle (NPER/BO‐PDT) is successfully prepared. NPER/BO‐PDT has the endoplasmic reticulum (ER) targeting ability, resulting in stimulated continuous reactive oxygen species‐based ER stress and cell death. Furthermore, NPER/BO‐PDT could better break the SRDD and amplify the effect of photodynamic‐immunotherapy in vitro and in vivo.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Acids / Bone cancer / Bone Neoplasms - metabolism / Cancer therapies / cascade targeting / Drug Delivery Systems / Endoplasmic reticulum / Endoplasmic Reticulum - metabolism / endoplasmic reticulum stress / Homeostasis / Humans / Hydroxyapatite / Immunotherapy / Ligands / Light / Nanoparticles / photodynamic‐immunotherapy / Photosensitizing Agents - metabolism / Photosensitizing Agents - pharmacology / Polymers / Reactive Oxygen Species - metabolism / step‐reduction delivery dilemma