Bacteria‐Mediated Tumor Therapy via Photothermally‐Programmed Cytolysin A Expression

Abstract

By leveraging the ability of bacteria to express therapeutic protein cytolysin A (ClyA) through plasmid transformation, a thermally‐activated biohybrid (TAB@Au) is constructed by biomineralizing gold nanoparticles (AuNPs) on the E. coli surface. Due to the feature of anaerobic bacteria homing to tumor microenvironments, the bacteria‐based antitumor vehicles can be efficaciously accumulated at tumor sites. Under NIR laser irradiation, the biomineralized AuNPs harvest transdermal photons and convert them into local heat for photothermal therapy. After that, the produced heat elicits the expression of ClyA for killing tumor cells. In vitro and in vivo experiments verify the conception that the current therapeutic modality greatly inhibits the proliferation of tumor cells. In terms of the spatial specificity and non‐invasiveness of NIR laser, the bacteria‐based phototherapy represents an appealing way for tumor therapy.

Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy

“…The transfer plasmid pET3a@adiA/ClyA/GFP was constructed based on a previously reported protocol with minor modifications (Table S1 , Supporting Information). [ 30 ] We recombinantly fused the gene fragment for ClyA containing the adiA promoter and GFP tag into the vector plasmid. The ClyA gene was derived from Salmonella typhimurium , and the translated protein has the ability of membrane perforations to damage tumor cells.…”

“…The excellent membrane perforation ability of ClyA caused significant cytotoxicity (Figure S4 , Supporting Information), which has been shown in our previous work. [ 30 ]…”

Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery

“…1A). Using biotin-streptavidin coupling allowed us to integrate artificial units onto viable bacteria without the need for harsh chemical or physical incubation processes that are required in most bacterial biohybrid conjugation approaches used in the literature (29)(30)(31). To characterize the efficiency of our coating method quantitatively, we performed flow cytometry analyses, which showed that 92.2% of the bacteria population (the number of biohybridized bacteria/total number of bacteria) was conjugated with mNPs (Fig.…”

Tailoring bismuth-based nanoparticles for enhanced radiosensitivity in cancer therapy

“…49,50 Cytolysin A (ClyA), secreted by some gut bacteria, has been reported to damage the cell cycle during the RT process. 51,52 Based on this, Pan et al used Escherichia coli MG1655 for ClyA protein overexpression (Bac), and chemically modified it onto Bi-based NP (BNP) to obtain Bac@BNP (Fig. 2c).…”