Mannosylated protamine as a novel DNA vaccine carrier for effective induction of anti-tumor immune responses.
Gene immunotherapy has been developed as a promising strategy for inhibition of tumor growth. In the study, mannosylated protamine sulphate (MPS) was used as a novel DNA vaccine carrier to enhance transfection efficiency and anti-tumor immune responses. Anti-GRP DNA vaccine (pGRP) was selected as a model gene and condensed by MPS to form MPS/pGRP nanoparticles. The cellular uptake and transfection efficiency of MPS/pGRP nanoparticles in macrophages were evaluated. The effect of the nanoparticles in enhancing GRP-specific humoral immune response was then evaluated by nasal vaccination of nanoparticles in mice. The results demonstrated that both the cellular uptake and transfection efficiency of MPS nanoparticles in macrophages were higher than those of protamine nanoparticles. MPS/pGRP nanoparticles stimulated the production of higher titers (3.9×10(3)) of specific antibodies against GRP than those of protamine/pGRP nanoparticles (6.4×10(2), p<0.01) and intramuscular injection pGRP solution (2.5×10(3), p<0.05). Furthermore, the inhibitory rate in MPS/pGRP nanoparticles group (65.80%) was significantly higher than that in protamine/pGRP nanoparticles group (35.13%) and pGRP solution group (43.39%). Hence, it is evident that MPS is an efficient targeting gene delivery carrier which could improve in vitro transfection efficiency as well as anti-tumor immunotherapy in mice.
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China.
Zhaoyan
Z
Zeng
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China.
Shuang
S
Dai
Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, School of Environmental Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, PR China.
Yan
Y
Jiao
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China.
Lei
L
Jiang
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China.
Yuekui
Y
Zhao
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China. Electronic address: bwangcpu@163.com.
Bo
B
Wang
Department of Pharmaceutics, China Pharmaceutical University, TongJiaXiang No. 24, Nanjing 210009, PR China. Electronic address: zongcpu@126.com.
Li
L
Zong
D000281:Administration, Intranasal; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007167:Immunotherapy / Q000379:methods; D007273:Injections, Intramuscular; D008264:Macrophages / Q000276:immunology; D008297:Male; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D011479:Protamines / Q000737:chemistry*; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D019496:Cancer Vaccines; D011479:Protamines; D019444:Vaccines, DNA; D008358:Mannose
Anti-tumor; DNA vaccine; Mannosylated protamine sulphate; Mucosal immunization; Nanoparticles