Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

• Published in: Vaccine Vol. 28; no. 36; pp. 5760 - 5767
• Main Authors: Kudela, Pavol, Koller, Verena Juliana, Lubitz, Werner
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.08.2010; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Antigen-presenting cells; Antineoplastic Agents - pharmacology; Applied microbiology; Bacteria; Bacterial ghosts; Bacteriology; Biological and medical sciences; Caco-2 Cells; Cancer; Cancer therapies; Cancer therapy; Cancer Vaccines; Cell Proliferation - drug effects; Cytotoxicity; Delivery system; Deoxyribonucleic acid; DNA; DNA - administration & dosage; Doxorubicin - pharmacology; Drug Delivery Systems; Drug dosages; E coli; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Transfer Techniques; Genetic Vectors; Gram-negative bacteria; Gram-Negative Bacteria - immunology; Humans; Immune system; Leukemia; Leukemia - drug therapy; Medical sciences; Melanoma; Melanoma - drug therapy; Microbiology; Miscellaneous; Oncology; Peptides; Phagocytosis; Probiotics; Proteins; Technological change; Toxic substances; Toxicity; Tumors; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); multi-drug resistance; Toxicity; Ag; tumor-associated antigen; Doxorubicin; LPS; BGs; GFP; advanced drug delivery system; dendritic cells; DCs; PAMPs; MDR; TLR; Toll-like receptor; Delivery system; APCs; antigen-presenting cells; Vaccine; antigen; ADDS; Dox; green fluorescent protein; pathogen-associated molecular patterns; TAA; Cancer therapy; lipopolysaccharide; bacterial ghosts; Bacterial ghosts; Antigen; Treatment; Bacteria; Malignant tumor; Cancer
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.06.087

Abstract Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.