NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy

Area of Science:

• Nanotechnology
• Materials Science
• Cancer Therapy

Background:

• Current copper-based chemotherapy faces limitations in rapid and substantial cytotoxic agent production within tumors.
• Existing methods struggle with efficient delivery and activation of copper ions and disulfiram (DSF).

Purpose of the Study:

• To develop a novel nanoreactor for rapid, light-triggered generation of cytotoxic copper-selenium-disulfiram complexes (Cu_2-xSe-ET) for enhanced *in situ* chemotherapy.
• To investigate the mechanism of burst-release and *in situ* chelation for improved anti-tumor efficacy.

Main Methods:

• Fabrication of a phase change material (PCM) encapsulated nanoreactor containing ultrasmall copper selenide (Cu_2-xSe) nanoparticles and DSF.
• Triggering the nanoreactor with second near-infrared (NIR-II) light to induce burst release and catalytic complex formation.
• Evaluating the anti-tumor activity and mechanism of Cu_2-xSe-ET, focusing on autophagy induction.

Main Results:

• The nanoreactor achieved rapid and massive *in situ* production of Cu_2-xSe-ET complexes upon NIR-II irradiation.
• Ultrasmall Cu_2-xSe nanoparticles facilitated direct chelation of DSF on defect sites, bypassing the need for free copper ion release.
• Cu_2-xSe-ET exhibited potent anti-tumor activity, comparable to CuET, through enhanced autophagy, attributed to its unique 2D-like structure.

Conclusions:

• The light-triggered cascade reactor enables explosive *in situ* generation of tumor-suppressive substances, presenting a promising nanoplatform for precise chemotherapy.
• The size and valence of Cu_2-xSe nanoparticles are critical for the efficient catalytic reaction and potent anti-tumor effects.
• This approach offers a novel strategy for developing advanced nanomedicines for targeted cancer treatment.