Porphyrin-based covalent organic framework with NIR absorption: Preparation, hyaluronic acid modification, and cascading a hypoxia-sensitive drug for synergistic therapy of cancer phototherapy/chemotherapy.

Porphyrins are popular photosensitizers for photodynamic therapy of diseases. However, the poor water solution and short absorption wavelengths of porphyrins limit their clinical application. In this work, a novel worm-like porphyrin covalent organic framework (Por-COF) with excellent dispersibility and near-infrared absorption was prepared via a facile method. First, a pH-responsive macromolecule was prepared using Schiff base bonds between porphyrin and terephthalaldehyde, and the spatial arrangement of macromolecules was controlled to prepare Por-COF. Second, the hypoxia-responsive drug tirapazamine (TPZ) and tumor-targeted hyaluronic acid (HA) were loaded to Por-COF through the electrostatic effect to prepare a multifunction nanomedicine (Por-COF@TPZ/HA) that could simultaneously produce abundant reactive oxygen species and high temperature via808 nm laser irradiation. TPZ was cascaded for the synergistic therapy of cancers. In vitro cytotoxicity showed that the inhibition rate of cell activity in the Por-COF@TPZ/HA + Laser group was 1.2 times higher than that in the Por-COF/HA + Laser group. In vivo experiments also demonstrated that the aggravated tumor hypoxia caused by photodynamic therapy could activate TPZ to achieve high-efficiency chemotherapy. Combined photodynamic-photothermal therapy and chemotherapy had an outstanding synergistic effect. This work provides a promising method for Por-COF preparation and a feasible strategy for the synergistic therapy of cancers.