Near‐Infrared II Light‐Triggered Robust Carbon Radical Generation for Combined Photothermal and Thermodynamic Therapy of Hypoxic Tumors

Abstract

Tumor hypoxia is a major cause of failure in cancer therapy, and there is almost no efficacious treatment for hypoxic tumors. Herein, an azo‐containing polymer (P2) is designed to encapsulate IR1061, and further covalently grafted with a tumor‐targeting tripeptide RGD to form P2@IR1061‐RGD NPs for combined photothermal and thermodynamic therapy (PTT/TDT) in the near‐infrared II (NIR II) biowindow (1000–1700 nm). Upon 1064 nm laser irradiation, IR1061 generates heat to break the azo bonds of P2, achieving robust carbon radical generation, which induces cancer cell death even under a hypoxic tumor microenvironment. RNA‐sequencing is first adopted to unveil the impact of combined PTT/TDT on the cell transcriptome and the corresponding pathways using 4T1 breast cancer cells. The dysregulated genes are involved in protein processing within the endoplasmic reticulum, cell cycle regulation, ubiquitin‐mediated proteolysis, and DNA replication pathways. The tumor inhibition rates on a 4T1 breast cancer model as well as on a patient‐derived xenograft model of hepatocellular carcinoma (PDXHCC) are 97% and 100%, and negligible systematic toxicity is observed. This study proposes the application of an azo‐containing polymer for safe and efficient combined PTT/TDT in the NIR II biowindow, as a promising strategy for clinical treatment of hypoxic tumors.

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

“…The development of optical agents for tumor phototheranostics has recently attracted great interest because they allow real‐time molecular diagnosis and parallel phototriggered therapy. [ 1 , 2 , 3 , 4 ] It requires these agents to simultaneously emitter infrared fluorescence to imaging and has photodynamic or photothermal capabilities. And photoactivated photothermal therapy (PTT) has been established as safe model for tumor ablation in many cancer indications.…”

Fluorescent nanodiamond – hyaluronate conjugates for target-specific molecular imaging

“…2e and f). 45 Moreover, HA-FND conjugates were well dispersed in water due to the HA compared to FNDs as shown on HR-TEM images with 50k magnication. In 800k magnication images, while only the crystal lattices of FND were visible, the amorphous coating layer of HA in HA-FND conjugate was also observed on the crystal plane of FND, indicating the successful conjugation of HA on the surface of FND.…”

A Versatile Pep-CPDs Nanoprobe for Rapid Detection of mTBI Biomarker in Clinical Instances and Safe Fluorescence Imaging In Vivo for Improved Weight-Drop Mouse Model

“…Water-soluble pep-CPDs were prepared in a one-step hydrothermal reaction performed in an autoclave at 200 °C for 8 h. As presented in Supplementary Figure S1A, transmission electron microscopy was used to visualize the structure characterization of the prepared CPDs with an average size of 5.1 nm. The FTIR spectrum of the CPDs had an apparent peak around 2,965 cm −1 , indicating the presence of -OH groups and a peak at 1,407 cm −1 showing the presence of the C=O group (Wang et al, 2020;Yang et al, 2020;Liu et al, 2021) (Supplementary Figure S1B). The peak at 1,640 cm −1 corresponded to c = c starching vibration.…”