TY - JOUR
T1 - Near-infrared light triggered activation of pro-drug combination cancer therapy and induction of immunogenic cell death
AU - Kang, Xuejia
AU - Cai, Yuxin
AU - Wang, Qi
AU - Wang, Chuanyu
AU - Chen, Wu
AU - Yang, Wen
AU - Suryawanshi, Amol
AU - Zhou, Gang
AU - Chen, Pengyu
AU - Li, Feng
N1 - Funding Information:
This work was financially supported by the following resources: Launch Innovation Award (F, Li), Auburn University start-up fund (F. Li), NIH MIRA R35GM133795 (P. Chen). We thank Dr. Melissa Boersma at Auburn University Mass Spectrometry Center for LC/MS analysis.
Funding Information:
This work was financially supported by the following resources: Launch Innovation Award (F, Li), Auburn University start-up fund (F. Li), NIH MIRA R35GM133795 (P. Chen). We thank Dr. Melissa Boersma at Auburn University Mass Spectrometry Center for LC/MS analysis.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9/25
Y1 - 2021/9/25
N2 - 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)2 in 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.
AB - 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)2 in 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.
KW - CuS nanoparticles
KW - Disulfiram prodrug
KW - Immunogenic cell death (ICD)
KW - Near-infrared laser
KW - Reactive oxygen species (ROS)
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U2 - 10.1016/j.ijpharm.2021.120972
DO - 10.1016/j.ijpharm.2021.120972
M3 - Article
C2 - 34363916
AN - SCOPUS:85113205208
SN - 0378-5173
VL - 607
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 120972
ER -
