Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment.
The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines' production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer.
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain.
Estela
E
Noguera-Ortega
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain.
Núria
N
Blanco-Cabra
Unitat de Patologia Murina i Comparada, Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Spain.
Rosa Maria
RM
Rabanal
Servei de Microscopia, Universitat Autònoma de Barcelona, Spain.
Alejandro
A
Sánchez-Chardi
Servei de Microscopia, Universitat Autònoma de Barcelona, Spain.
Mónica
M
Roldán
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain.
Sandra
S
Guallar-Garrido
Bacterial Infections and Antimicrobial Therapy group, Institute for Bioengineering of Catalonia (IBEC), Spain.
Eduard
E
Torrents
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain.
Marina
M
Luquin
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain.
Esther
E
Julián
D000818:Animals; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D016207:Cytokines; D004655:Emulsions; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D050296:Microbial Viability; D009161:Mycobacterium / Q000276:immunology / Q000502:physiology*; D000069463:Olive Oil / Q000737:chemistry / Q000494:pharmacology; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D016207:Cytokines; D004655:Emulsions; D005353:Fibronectins; D000069463:Olive Oil