Strategically engineered Au(I) complexes for orchestrated tumor eradication via chemo-phototherapy and induced...

Area of Science:

• Medicinal Chemistry
• Nanotechnology
• Oncology

Background:

• Cancer remains a leading global cause of mortality, with many types lacking effective treatments.
• There is a critical need for innovative, targeted therapies to improve patient outcomes.
• Current treatments often face challenges with efficacy and specificity.

Purpose of the Study:

• To design and synthesize novel gold(I) complexes for targeted cancer treatment.
• To investigate the potential of these complexes in chemo-phototherapy and inducing immunogenic cell death.
• To evaluate a specific complex for tumor imaging, endoplasmic reticulum targeting, and therapeutic efficacy.

Main Methods:

• Synthesis and characterization of a series of gold(I) complexes (1-4) with tailored ligand structures.
• In vitro and in vivo studies using female mice models to assess therapeutic potential.
• Mechanistic studies involving endoplasmic reticulum targeting, reactive oxygen species (ROS) production, and thioredoxin reductase (TrxR) inhibition.

Main Results:

• Complex 4 demonstrated proficiency in tumor-specific imaging and endoplasmic reticulum targeting.
• The gold(I) complex exhibited significant therapeutic capabilities in vivo.
• Anticancer effects were attributed to synergistic inhibition of thioredoxin reductase, ROS generation, and induction of immunogenic cell death.

Conclusions:

• A robust gold(I) complex was developed, integrating chemo-phototherapy and immunogenic cell death induction.
• Complex 4 shows promise as a multifunctional agent for cancer imaging and treatment.
• This strategy offers a valuable platform for developing advanced therapeutic agents against cancer.