title: 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.
authors: †Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors: Qinglian
authors: Q
authors: Hu
authors: †Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors: Min
authors: M
authors: Wu
authors: ‡College of Animal Science, Zhejiang University, Hangzhou 310028, China.
authors: Chun
authors: C
authors: Fang
authors: ‡College of Animal Science, Zhejiang University, Hangzhou 310028, China.
authors: Changyong
authors: C
authors: Cheng
authors: †Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors: Mengmeng
authors: M
authors: Zhao
authors: ‡College of Animal Science, Zhejiang University, Hangzhou 310028, China.
authors: Weihuan
authors: W
authors: Fang
authors: §Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
authors: Paul K
authors: PK
authors: Chu
authors: ∥School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors: Yuan
authors: Y
authors: Ping
authors: †Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors: Guping
authors: G
authors: Tang
mesh_terms: D000284:Administration, Oral; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D012475:Salmonella / Q000502:physiology*; D014169:Transformation, Bacterial; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D019496:Cancer Vaccines; D020099:Coated Materials, Biocompatible; D053769:Nanocapsules; D019444:Vaccines, DNA
keywords: Salmonella; acid tolerance; cationic polymer; hybrid living material; phagosomal escape; vaccine delivery