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Theranostics 2022; 12(1):396-409. doi:10.7150/thno.67036 This issue Cite

Research Paper

A hypoxia-responsive supramolecular formulation for imaging-guided photothermal therapy

Tian-Xing Zhang^1,#, Xiaoxue Hou^2,#, Yong Kong³, Fan Yang³, Yu-Xin Yue¹, Muhammad Raza Shah⁴, Hua-Bin Li¹, Fan Huang^2✉, Jianfeng Liu^2✉, Dong-Sheng Guo^1✉

1. College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, China.
2. Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, Institute of Radiation Medicine Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China.
3. Research Institute of Petroleum Engineering, Sinopec, Beijing 100101, China.
4. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan.
# These authors contributed equally to this work.

✉ Corresponding authors: Fan Huang, Prof., E-mail: huangfanac.cn. Jianfeng Liu, Prof., E-mail: liujianfengac.cn. Dong-Sheng Guo, Prof., E-mail: dshguoedu.cn.

Abstract

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs.

Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo.

Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo.

Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

Keywords: supramolecular chemistry, photothermal therapy, hypoxia, calixarene, IR780

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