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. 2022 Oct 24;13:6321. doi: 10.1038/s41467-022-34036-8

Fig. 1. Working mechanism and preparation and characterization of the hydrogel-based bacteria protein cage delivery system.

Fig. 1

a The GSDMD proteins were crosslinked into protein cages and then conjugated on the surface of attenuated Salmonella typhimurium (designated VNP-GD). The ESCRT inhibitor was loaded in the dextran nanoparticles (designated EI-NP). Two formulations, an injectable hydrogel and a cell patch, were developed to co-load VNP-GD and EI-NP to treat primary tumors through local administration and inoperable cancer through implantation. b The underlying mechanism of tumor pyroptosis triggered by VNP-GD and further enhanced by EI-NP. Firstly, after the invasion of the VNP-GD into the tumor, the GSDMD protein would be released upon GSH stimulation, and the abundant flagella on the surface of bacteria could activate the caspase 1 into cleaved caspase 1, which will further cleave the GSDMD protein to the N-terminal GSDMD that will multimerize and perforate the cell membrane, initiating cell pyroptosis. Secondly, the released ESCRT inhibitor from EI-NP could effectively block the calcium influx to inhibit the ESCRT III-mediated membrane repair to enhance the tumor pyroptosis. c Particle size and transmission electronic microscope (TEM) image (inserted) of the protein cages (scale bar = 100 nm). d Representative TEM image of the protein cage-conjugated VNP bacteria (VNP-GD, scale bar = 200 nm). The experiments were repeated three times independently. e Confocal images of the conjugation of the protein cage (labeled with Rhodamine B) on the surface of the VNP bacteria (labeled with Hoechst), scale bar = 10 μm. The experiments were repeated three times independently. f Cumulative release of the protein from the bacteria protein cage with or without the trigger of GSH (10 mM). Data are presented as mean ± s.d. (n = 3 biologically independent samples). g Particle size and transmission electronic microscope (TEM) image (inserted) of the EI-NP (scale bar = 500 nm). h ESCRT inhibitor release profile from the dextran nanoparticle (EI-NP) at predetermined time points. Data are presented as mean ± s.d. (n = 3 biologically independent samples). Source data are provided as a Source Data file.