Engineering Nanoparticle-Coated Bacteria as Oral DNA Vaccines for Cancer Immunotherapy

Abstract

Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.

An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

“…NE were prepared under an identical protocol but without the addition of chitosan and HCl in the aqueous phase. To prepare different concentrations of 3OC6HSL-loaded NC, 500 L of an 80 mg/mL ethanolic lecithin solution was mixed with 10 mL of different concentration (10,20,40,60,120,200 and 400 nM) ethanolic 3OC6HSL solutions and 125 µL Miglyol 812 N as the organic phase.…”

“…Other nanomaterials bearing a positively-charged surface, such as diamond nanoparticles, bind closely to the surface of bacteria [7]. On the other hand, conjugation of targeting ligands such as aptamers [8], peptides [9], or DNA [10], also confers nanomaterials with targeting capacity toward microorganisms [11][12][13]. Different types of microscopy (e.g., TEM, AFM, SEM) and molecular biology techniques offer powerful approaches to probe bacteria-nanomaterials interactions [14][15][16][17][18][19].…”

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

“…This oral vaccine encodes for Vascular endothelial growth factor receptor 2 (VEGFR2). When a B16 melanoma tumor model was treated with this system, higher CD8+ was observed when compared with the controls [53]. These mice exhibited high concentration of cytokines such as TNF-α, IFN, and IL-12.…”

Improving Vaccine and Immunotherapy Design Using Biomaterials

“…In another approach, live attenuated bacteria were modified with self-assembled NPs containing DNA encoding antiangiogenic factors. The bacteria served as an adjuvant to activate T cells, while the DNA restrained angiogenesis [59]. …”