Bacteria-based cascade in situ near-infrared nano-optogenetically induced photothermal tumor therapy.

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  • Additional Information
    • Source:
      Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
    • Publication Information:
      Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
    • Subject Terms:
      Photothermal Therapy*/methods ; Escherichia coli*/genetics ; Nanoparticles*/chemistry ; Optogenetics*/methods; Animals ; Mice ; Cell Line, Tumor ; Mice, Inbred BALB C ; Infrared Rays ; Female ; Neoplasms/therapy ; Humans ; Phototherapy/methods
    • Abstract:
      Rationale: Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcN αHL -UCNPs) for enhanced tumor therapy. Methods: EcN αHL -UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcN αHL -UCNPs were determined in both H22 and 4T1 tumors. Results: The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an in situ photothermal agent in tumors. The in situ formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcN αHL -UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response. Conclusion: Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.
      Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
      (© The author(s).)
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    • Contributed Indexing:
      Keywords: NIR-optogenetics; bacteria; in situ photothermal agents; tumor therapy; α-hemolysin
    • Publication Date:
      Date Created: 20240913 Date Completed: 20240913 Latest Revision: 20240914
    • Publication Date:
      20240914
    • Accession Number:
      PMC11388082
    • Accession Number:
      10.7150/thno.98097
    • Accession Number:
      39267783