Near-infrared light triggered activation of pro-drug combination cancer therapy and induction of immunogenic cell death.

Abstract

Disulfiram copper complex [Cu(DDC)2] nanoparticles have been explored as promising anticancer agents but with concerns of toxic side effects. To improve tumor specificity and enhance anticancer efficacy, we developed a novel [copper sulfide nanoparticle (CuS NP) + disulfiram prodrug (DQ) micelle + near-infrared (NIR) laser] (CDL) combination therapy. DQ, a reactive oxygen species (ROS)-responsive prodrug, can be selectively activated at the tumor site with elevated ROS to release DDC and form Cu(DDC)2in situ. The CuS NP + NIR laser treatment can effectively increase the intra-tumor ROS levels and efficiently activate the DQ prodrug. The CDL therapy kills cancer cells through multiple mechanisms, including ROS amplification cascade and Cu(DDC)2 chemotherapy. NIR light-triggered tumor-specific "nontoxic-to-toxic" transition can significantly improve the specificity of anticancer effects and reduce systemic toxicity. Also, CDL therapy can effectively induce immunogenic cell death (ICD) and has the potential of eliciting antitumor immunity.

• Authors: Xuejia Kang, Yuxin Cai, Qi Wang, Chuanyu Wang, Wu Chen, Wen Yang, Amol Suryawanshi, Gang Zhou, Pengyu Chen, Feng Li
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 607 Pg. 120972 (Sep 25 2021) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 34363916 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Drug Combinations
• Prodrugs
• Copper

Topics

• Cell Line, Tumor
• Copper
• Drug Combinations
• Immunogenic Cell Death
• Infrared Rays
• Nanoparticles
• Neoplasms (drug therapy)
• Prodrugs