Image-Guided Photothermal and Immune Therapy of Tumors via Melanin-Producing Genetically Engineered Bacteria

Small. 2024 Jun;20(26):e2305764. doi: 10.1002/smll.202305764. Epub 2024 Feb 17.

Abstract

Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, a natural photothermal agent, into tumors using genetically engineered bacteria for image-guided photothermal and immune therapy is developed. An Escherichia coli MG1655 is transformed with a recombinant plasmid harboring a tyrosinase gene to produce melanin nanoparticles. Melanin-producing genetically engineered bacteria (MG1655-M) are systemically administered to 4T1 tumor-bearing mice. The tumor-targeting properties of MG1655-M in the hypoxic environment integrate the properties of hypoxia targeting, photoacoustic imaging, and photothermal therapeutic agents in an "all-in-one" manner. This eliminates the need for post-modification to achieve image-guided hypoxia-targeted cancer photothermal therapy. Tumor growth is significantly suppressed by irradiating the tumor with an 808 nm laser. Furthermore, strong antitumor immunity is triggered by PTT, thereby producing long-term immune memory effects that effectively inhibit tumor metastasis and recurrence. This work proposes a new photothermal and immune therapy guided by an "all-in-one" melanin-producing genetically engineered bacteria, which can offer broad potential applications in cancer treatment.

Keywords: genetically engineered bacteria; melanin; photothermal therapy; tumors.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Genetic Engineering
  • Immunotherapy* / methods
  • Melanins*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Neoplasms / therapy
  • Phototherapy / methods
  • Photothermal Therapy / methods

Substances

  • Melanins