- Email: [email protected]
Nanoparticle-coated Salmonella as Oral DNA Vaccines for Cancer Immunotherapy
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
phosphatidylethanolamine-poly(N-isopropyl acrylamide)40 (PE− p(NIPAM)40 −FA) in different ratios [3]. Apart from PDT, here a chemotherautic DNA interacting drug doxorubicin (Dox) loaded VNS was used to investigate the Dox release at different temperature and pH conditions. Antitumor effect of the released Dox is also invetigated using the KB squamous carcinoma cell lines. The cellular uptake studies indicated that the intracellular drug release of Dox-loaded VNS was obviously increased at pH 6.0 and 37 oC. The folic acid decorated pH and temperture dual stimuli-responsive VNS may serve as a promising system for cell specific anti-tumor drug delivery (Fig. 1).
Fig. 1. Illustration of Dox-loaded vesicular nanosphere for site specific drug release.
Keywords: drug delivery, lipopolymer, polypeptide, stimuli-responsive, vesicular nanosphere
e179
have been successfully exploited as vectors for the oral delivery of vaccines. As compared to intravenous vaccination, oral delivery of vaccines mediated by attenuated Salmonella is cost-effective and less toxic. Nevertheless, the oral vaccination of live attenuated Salmonellae often results in low infection efficency, primarily owing to the digestion of Salmonellae in the acidic stomach environment [1]. Furthermore, live attenuated Salmonellae are inherently lack the ability to escape phagosomes once they are captured by phagocytes, which has severely restricted its replication following the invasion into intestinal mucosa. As a result, the induction of MHC class-I-restricted immune response is largely limited, as a key reason for the failure of DNA vaccination against tumor formation and progression. In light of these challenges, we herein report a simple strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccines for efficacious cancer immunotherapy [2]. By coating live attenuated Salmonella with polymer/DNA nanoparticles, we found the coating layer is able to effectively enhance escape phagosomes, and significantly improve the acid tolerance of Salmonella in stomach and intestines (Fig. 1). Most importantly, the oral vaccination of DNA encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) mediated by these nanoparticle-coated bacteria showed remarkable T cell activation and cytokine production, thereby achieving successful inhibition of tumor growth as a result of angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live attenuated bacteria with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile oral DNA vaccines for cancer immunotherapy.
Acknowledgements This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (2015R1D1A1A09057372). The authors also thank BK21 PLUS Program for partial financial support. References [1] J.V. John, R.P. Johnson, M.S. Heo, B.K. Moon, S.J. Byeon, I. Kim, Polymer-blockpolypeptides and polymer-conjugated hybrid materials as stimuli-responsive nanocarriers for biomedical applications, J. Biomed Nanotechnol. 11 (2015) 1-39. [2] J.V. John, Y.-I. Jeong, R.P. Johnson, C.-W. Chung, H. Park, D.H. Kang, J.K. Cho, Y. Kim, I. Kim, Folic acid-tethered poly(N-isopropylacrylamide)-phospholipid hybrid nanocarriers for targeted drug delivery, J. Mater. Chem. B 3 (2015) 8268-8278. [3] J.V. John, C.-W. Chung, R.P. Johnson, Y.-I. Jeong, K.-D. Chung, D.H. Kang, H. Suh, H. Chen, I. Kim, Dual stimuli-responsive vesicular nanospheres fabricated by lipopolymer hybrids for tumor-targeted photodynamic therapy, Biomacromolecules 17 (2016) 20-31.
doi:10.1016/j.jconrel.2017.03.353
Nanoparticle-coated Salmonella as Oral DNA Vaccines for Cancer Immunotherapy Yuan Pinga,⁎, Qinglian Hub, Min Wub, Guping Tangb,⁎, Chuanbin Wua a School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China b Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Ping), [email protected] (G. Tang) Although oral delivery of DNA vaccine has drawn extensive attentions and represents one of the most promising approaches for cancer immunotherapy; however, the low efficiency of DNA transfection is the major bottleneck that severly hampers the efficacious immune response. Live bacterial strains, such as attenuated Salmonella,
Fig. 1. Schematic Illustration of engineering nanoparticle-coated bacteria for cancer vaccination.
Keywords: vaccine delivery, nanomedicine, Salmonellae, phagosomal escape References [1] K. W. Leong, H. W. Sung, Nanoparticle- and biomaterials-mediated oral delivery for drug, gene, and immunotherapy, Adv. Drug Deliv. Rev. 65 (2013) 757-758. [2] Q. Hu, M. Wu, C. Fang, C. Cheng, M. Zhao, W. Fang, P. K. Chu, Y. Ping, G. Tang, Engineering nanoparticle-coated bacteria as oral dna vaccines for cancer immunotherapy, Nano Lett. 15 (2015) 2732-2739.
doi:10.1016/j.jconrel.2017.03.354
siRNA mediated inhibition of pancreatic tumor growth in vitro and in vivo Yuanyu Huanga,⁎, Xingyu Jinb, Shuquan Zhenga, Shan Gaob,⁎⁎, Zicai Lianga a Institute of Molecular Medicine, Peking University, Beijing 100871, China
phosphatidylethanolamine-poly(N-isopropyl acrylamide)40 (PE− p(NIPAM)40 −FA) in different ratios [3]. Apart from PDT, here a chemotherautic DNA interacting drug doxorubicin (Dox) loaded VNS was used to investigate the Dox release at different temperature and pH conditions. Antitumor effect of the released Dox is also invetigated using the KB squamous carcinoma cell lines. The cellular uptake studies indicated that the intracellular drug release of Dox-loaded VNS was obviously increased at pH 6.0 and 37 oC. The folic acid decorated pH and temperture dual stimuli-responsive VNS may serve as a promising system for cell specific anti-tumor drug delivery (Fig. 1).
Fig. 1. Illustration of Dox-loaded vesicular nanosphere for site specific drug release.
Keywords: drug delivery, lipopolymer, polypeptide, stimuli-responsive, vesicular nanosphere
e179
have been successfully exploited as vectors for the oral delivery of vaccines. As compared to intravenous vaccination, oral delivery of vaccines mediated by attenuated Salmonella is cost-effective and less toxic. Nevertheless, the oral vaccination of live attenuated Salmonellae often results in low infection efficency, primarily owing to the digestion of Salmonellae in the acidic stomach environment [1]. Furthermore, live attenuated Salmonellae are inherently lack the ability to escape phagosomes once they are captured by phagocytes, which has severely restricted its replication following the invasion into intestinal mucosa. As a result, the induction of MHC class-I-restricted immune response is largely limited, as a key reason for the failure of DNA vaccination against tumor formation and progression. In light of these challenges, we herein report a simple strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccines for efficacious cancer immunotherapy [2]. By coating live attenuated Salmonella with polymer/DNA nanoparticles, we found the coating layer is able to effectively enhance escape phagosomes, and significantly improve the acid tolerance of Salmonella in stomach and intestines (Fig. 1). Most importantly, the oral vaccination of DNA encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) mediated by these nanoparticle-coated bacteria showed remarkable T cell activation and cytokine production, thereby achieving successful inhibition of tumor growth as a result of angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live attenuated bacteria with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile oral DNA vaccines for cancer immunotherapy.
Acknowledgements This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (2015R1D1A1A09057372). The authors also thank BK21 PLUS Program for partial financial support. References [1] J.V. John, R.P. Johnson, M.S. Heo, B.K. Moon, S.J. Byeon, I. Kim, Polymer-blockpolypeptides and polymer-conjugated hybrid materials as stimuli-responsive nanocarriers for biomedical applications, J. Biomed Nanotechnol. 11 (2015) 1-39. [2] J.V. John, Y.-I. Jeong, R.P. Johnson, C.-W. Chung, H. Park, D.H. Kang, J.K. Cho, Y. Kim, I. Kim, Folic acid-tethered poly(N-isopropylacrylamide)-phospholipid hybrid nanocarriers for targeted drug delivery, J. Mater. Chem. B 3 (2015) 8268-8278. [3] J.V. John, C.-W. Chung, R.P. Johnson, Y.-I. Jeong, K.-D. Chung, D.H. Kang, H. Suh, H. Chen, I. Kim, Dual stimuli-responsive vesicular nanospheres fabricated by lipopolymer hybrids for tumor-targeted photodynamic therapy, Biomacromolecules 17 (2016) 20-31.
doi:10.1016/j.jconrel.2017.03.353
Nanoparticle-coated Salmonella as Oral DNA Vaccines for Cancer Immunotherapy Yuan Pinga,⁎, Qinglian Hub, Min Wub, Guping Tangb,⁎, Chuanbin Wua a School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China b Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Ping), [email protected] (G. Tang) Although oral delivery of DNA vaccine has drawn extensive attentions and represents one of the most promising approaches for cancer immunotherapy; however, the low efficiency of DNA transfection is the major bottleneck that severly hampers the efficacious immune response. Live bacterial strains, such as attenuated Salmonella,
Fig. 1. Schematic Illustration of engineering nanoparticle-coated bacteria for cancer vaccination.
Keywords: vaccine delivery, nanomedicine, Salmonellae, phagosomal escape References [1] K. W. Leong, H. W. Sung, Nanoparticle- and biomaterials-mediated oral delivery for drug, gene, and immunotherapy, Adv. Drug Deliv. Rev. 65 (2013) 757-758. [2] Q. Hu, M. Wu, C. Fang, C. Cheng, M. Zhao, W. Fang, P. K. Chu, Y. Ping, G. Tang, Engineering nanoparticle-coated bacteria as oral dna vaccines for cancer immunotherapy, Nano Lett. 15 (2015) 2732-2739.
doi:10.1016/j.jconrel.2017.03.354
siRNA mediated inhibition of pancreatic tumor growth in vitro and in vivo Yuanyu Huanga,⁎, Xingyu Jinb, Shuquan Zhenga, Shan Gaob,⁎⁎, Zicai Lianga a Institute of Molecular Medicine, Peking University, Beijing 100871, China