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

Abstract

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.

Global Trends and Research Progress of Photodynamic Therapy in Skin Cancer: A Bibliometric Analysis and Literature Review

“…1,2 With the rapid and excessive formation of reactive oxygen species (ROS), cell killing, microvascular damage effects and local immune responses were triggered through the lipid peroxidation and DNA damage, manifested as apoptosis, necrosis, or immunogenic cell death. [3][4][5][6][7][8] Over the past 30 years, PDT has been increasingly applied to treat various solid tumors, including brain, lung, gastrointestine, bone, bladder, prostate, breast, cervix, ovary, etc. 9,10 For the skin is the outermost layer of the body which is convenient for the irradiation of the light, Dermatology is a department with plenty of opportunities of PDT application, for the treatment of diseases from acne, naevus flammeus, to skin cancer.…”

A NIR‐II Fluorescent PolyBodipy Delivering Cationic Pt‐NHC with Type II Immunogenic Cell Death for Combined Chemotherapy and Photodynamic Immunotherapy

“…[ 8 ] ICD is a particular modality of cell death that can be triggered by selective anticancer chemotherapeutics such as oxaliplatin (Oxa), [ 9 ] doxorubicin, [ 10 ] etc. photodynamic therapy (PDT), [ 11 ] and radiation therapy. [ 12 ] Tumor cells undergoing ICD can induce an adaptive anticancer immune response including the release or exposure of damage associated molecular patterns (DAMPs) by tumor cells that stimulate the attraction, activation and maturation of dendritic cells (DCs) and eventually the antigen‐specific priming of cytotoxic T lymphocytes.…”

Polyphotosensitizer‐Based Nanoparticles with Michael Addition Acceptors Inhibiting GST Activity and Cisplatin Deactivation for Enhanced Chemotherapy and Photodynamic Immunotherapy

“…[ 12 ] Results have shown that tumor cells undergoing type II ICD can release damage‐associated molecular patterns (DMAPs): calreticulin (CRT) exposed on their cell surface, adenosine triphosphate (ATP) secreted, and high mobility‐group protein box 1 (HMGB1) released. [ 13 ] Recent studies have shown that PDT could promote the apoptosis of tumor cells. Moreover, PDT could promote the uptake and presentation of tumor‐associated antigens by antigen‐presenting cells, reactivate the recognition and attack of tumor cells by T cells, and allow more infiltration of CD8 + T cells, thereby transforming immune “cold tumors” into immune “hot tumors” and finally improving the responses to immune checkpoint inhibitors.…”