title: Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.
abstract: Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p < 0.01) and intramuscular administration of a pGRP solution (p < 0.05) to mice. In addition, immunization with MCS/pGRP nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p < 0.01) or that in the pGRP group (1.12 ± 0.37 g) (p < 0.05). Cell binding and cellular uptake results indicated that MCS/pGRP nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.
authors.affiliation: School of Pharmacy, China Pharmaceutical University , TongJiaXiang No. 24, Nanjing 210009, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yao
authors.forename: Yixing
authors.initials: Y
authors.lastname: Peng
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Du
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Zong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D007167:Immunotherapy; D008297:Male; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009297:Nasal Mucosa / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D014612:Vaccines; D048271:Chitosan; D008358:Mannose