A polymer coating applied to Salmonella prevents the binding of Salmonella‐specific antibodies

Abstract

The use of Salmonella as a potential antitumor agent has been investigated, but innate immunity against this bacterium reduces the efficacy of its tumor-targeting and antitumor activities. The purpose of this study was to investigate the modulation of the tumor-targeting efficiency of Salmonella enterica serovar choleraesuis by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride) (PAH), designated PAH-S.C. To evaluate this modulation, we used naïve mice and mice immunized with Salmonella to study the role of the preexisting immune response to the antitumor activity of PAH-S.C. When anti-Salmonella antibodies were present, the invasion activity, cytotoxicity, and gene transfer of Salmonella was significantly decreased, both in vitro and in vivo. Treatment with PAH-S.C. resulted in delayed tumor growth and enhanced survival in immunized mice. Furthermore, immunohistochemical studies of the tumors revealed the infiltration of neutrophils and macrophages in immunized mice treated with PAH-S.C. These results indicate that Salmonella encapsulation effectively circumvented the Salmonella-specific immune response.

Salmonella as an Innovative Therapeutic Antitumor Agent

“…The bacterial cell wall is negatively charged due to the presence of either teichoic acid in gram-positive bacteria or LPS in gram-negative bacteria. Positively charged polyelectrolytes can bond to negatively charged Salmonella surfaces to form thin films that circumvent preexisting immunity against Salmonella [35]. The encapsulation of Salmonella in polymer reduces the antigenicity of Salmonella following in vivo delivery.…”

“…The induction of inflammation cytokines ( i.e. , IL-1β and TNF-α) in mice treated with Salmonella was increased by 1.5–4.5-fold compared with induction by polymer-modified Salmonella treatment [35]. Polymer also can provide a useful platform for the chemical modification of Salmonella , perhaps allowing other chemotherapeutic drugs to bind to tumor-targeting Salmonella .…”

Salmonella mediated the hemagglutinating virus of Japan-envelope transfer suppresses tumor growth

“…The presence of lipopolysaccharide (LPS) in the cell wall of gram-negative bacteria results in the negatives surface charged of Salmonella . The negatively charged bacterial surfaces can absorb the positively charged polyelectrolytes to form a complex [26]. Here, this study demonstrates that the oncolytic virus delivery into the tumor site by using tumor-targeting Salmonella to enhance the therapeutic index.…”

“…Previously, the masking of Salmonella with a polymer reduced the antigenicity of Salmonella [26]. Herein, we attempted to encapsulate the hemagglutinating virus of Japan-envelope (HVJ-E) into poly (allylamine hydrochloride) (PAH) and change the surface charged of HVJ-E [26].…”

“…Herein, we attempted to encapsulate the hemagglutinating virus of Japan-envelope (HVJ-E) into poly (allylamine hydrochloride) (PAH) and change the surface charged of HVJ-E [26]. Polymers shield HVJ-E from the hemagglutination activity after systemic administration [26]. The presence of lipopolysaccharide (LPS) in the cell wall of gram-negative bacteria results in the negatives surface charged of Salmonella .…”