Near-Infrared-II\nPhotoactivated Iron(III) Complexes\nfor Highly Efficient RNS and ROS Synergistic Therapy

Reactive nitrogen species (RNS) are more lethal than\nreactive oxygen\nspecies (ROS), which gives them a very promising future in the field\nof cancer treatment. However, there are still a few drugs available\nfor RNS generation. In this work, two 5th-order nonlinear optical\nmaterials, FB-Fe(III)/SNP@PEG and FB-Fe(II)-FB/SNP@PEG, are synthesized.\nThe outstanding nonlinear optical properties of FB-Fe(III)/SNP@PEG\nhelp to achieve generation of bounteous superoxide anions (O<sub>2</sub><sup>•–</sup>) in deep tissues, while sodium nitroprusside\n(SNP) provides NO in the body, both of which are prerequisites for\nRNS generation. Meanwhile, type I and type II ROS were also generated\nunder irradiation of a 1600 nm laser. Based on the synergistic effect\nof ROS and RNS, FB-Fe(III)/SNP@PEG induced mitochondrial damage and\nDNA fragmentation and inhibited tumor cells through apoptosis, possessing\nbetter therapeutic effects than FB-Fe(II)-FB/SNP@PEG. This work put\nforward an innovative strategy to achieve the cooperative release\nof RNS and ROS in deep tissues, which provides insights and ideas\nfor applying nonlinear optical materials to RNS therapy.