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

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Organic small-molecule dyes are promising photothermal agents (PTAs) for imaging and photothermal therapy (PTT).
• Hydrophobicity, photodegradation, and low signal-to-noise ratio limit their clinical application.
• Stimuli-responsive macrocyclic hosts can potentially overcome these limitations.

Purpose of the Study:

• To develop a novel supramolecular photothermal therapy (PTT) formulation using a stimuli-responsive macrocyclic host.
• To enhance the properties of organic small-molecule PTAs for improved theranostic applications.
• To evaluate the hypoxia tumor-selective imaging and PTT efficacy of the novel formulation.

Main Methods:

• Synthesized sulfonated azocalix[4]arene (SAC4A) as a hypoxia-responsive macrocyclic host.
• Constructed the supramolecular nanoformulation IR780@SAC4A using a grinding method.
• Evaluated solubility, photostability, photothermal conversion, and in vitro/in vivo imaging-guided PTT efficacy.

Main Results:

• The IR780@SAC4A formulation significantly enhanced the solubility, photostability, and photothermal conversion of the PTA.
• Achieved good imaging-guided PTT efficacy both in vitro and in vivo.
• Demonstrated hypoxia tumor-selective imaging capabilities.

Conclusions:

• Supramolecular PTT strategies offer a promising approach for cancer theranostics.
• This supramolecular method is applicable to various PTAs, enabling the development of smart PTT formulations.
• The developed formulation overcomes key limitations of traditional organic small-molecule PTAs.