Bioengineering Living Biohybrid Therapeutics for Synergistic H₂S Gaseous-Photothermal Cancer Eradication

Area of Science:

• Biotechnology
• Nanotechnology
• Cancer Therapy

Background:

• Hydrogen sulfide (H₂S) gas therapy shows promise for cancer treatment due to its efficacy and biosafety.
• Current H₂S delivery methods lack tumor specificity and controlled release, limiting their clinical application.

Purpose of the Study:

• To develop a novel living therapeutic biohybrid for synergistic H₂S gas and photothermal cancer treatment.
• To engineer bacteria for in situ H₂S production and self-mineralization of copper sulfide (CuS) nanoparticles.

Main Methods:

• Engineered *Vibrio natriegens* bacteria were developed to produce H₂S and synthesize CuS nanoparticles, forming Bac@CuS biohybrids.
• The Bac@CuS biohybrids were investigated for their ability to inhibit cancer cell mitochondria via H₂S and induce hyperthermia through photothermal effects.
• In vivo studies were conducted using a breast tumor-bearing mouse model.

Main Results:

• The engineered Bac@CuS biohybrids demonstrated synergistic H₂S gas and photothermal effects, leading to increased reactive oxygen species and apoptosis in cancer cells.
• In vivo studies showed excellent biocompatibility and achieved a 95.4% tumor inhibition rate in the mouse model.
• The biohybrid platform successfully integrated synthetic biology and nanotechnology for targeted cancer therapy.

Conclusions:

• The developed Bac@CuS living biohybrids offer a novel and effective platform for synergistic cancer treatment.
• This approach overcomes limitations of conventional H₂S delivery by enhancing tumor specificity and controlled release.
• The integration of engineered microbes and nanoparticles presents a promising strategy for future cancer eradication therapies.