title: Programmed nanoparticles for combined immunomodulation, antigen presentation and tracking of immunotherapeutic cells.
abstract: We report programmed nanoparticles (pNPs) that can tailor the immunotherapeutic function of primary bone marrow-derived dendritic cells (BMDCs) by ex vivo combined immunomodulation and track the in vivo migration of them after injection into body. Because DCs are the most effective antigen-presenting cells (APCs) that are able to present the antigens to T cells that contribute to tumor rejection, the maturation and monitoring of therapeutic DCs are essential for the efficient cancer immunotherapy. For combined immunomodulation of DCs, poly (lactic-co-glycolic acid) (PLGA) NPs containing both small interfering RNA (siRNA) for the knock-down of immune-suppressor gene (signal transducer and activator of transcription-3, STAT3) of DCs and an immune response modifier (imiquimod, R837) for the activation of DCs through the toll-like receptor 7 (TLR7) were developed. To deliver tumor antigen-specific information to DCs ex vivo and track the migration of DCs in vivo, another type of PLGA NPs containing tumor model antigen (ovalbumin, OVA) and near-infrared (NIR) fluorophores (indocyanine green, ICG) were also fabricated. These pNPs were taken up efficiently by DCs and various cytokines were expressed in matured DCs. DCs treated with pNPs also efficiently presented antigen-peptide to CD8 OVA 1.3 T cells through cross-presentation. Immunization of mice with these pNPs-treated DCs induced OVA-specific cytotoxic T lymphocytes (CTL) activity against the EG7-OVA tumor model and inhibited tumor growth efficiently. In addition, the migration of PLGA NPs-treated DCs to lymph nodes was monitored by NIR imaging technique. These multifunctional pNPs represent a promising technology for the combined immunomodulation and antigen-specific tumor therapy.
authors.affiliation: Graduate School and Department of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Min Beom
authors.initials: MB
authors.lastname: Heo
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001483:Base Sequence; D005260:Female; D020868:Gene Silencing; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: Antigen delivery; Dendritic cells; Immunotherapy; Nanoparticles; siRNA