title: Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo.
abstract: Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs)-antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT-OVA (~386nm), bearing net positive charge (5.8mV), or short MWNTs-OVA (~122nm) of increasing negative charges (-23.4, -35.8 or -39mV). Compared to the short MWNTs-OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system.
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Hatem A F M
authors.initials: HA
authors.lastname: Hassan
authors.affiliation: Immunoregulation Laboratory, MRC Center for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Lesley
authors.initials: L
authors.lastname: Smyth
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Noelia
authors.initials: N
authors.lastname: Rubio
authors.affiliation: Immunoregulation Laboratory, MRC Center for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Kulachelvy
authors.initials: K
authors.lastname: Ratnasothy
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Julie T-W
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Sukhvinder S
authors.initials: SS
authors.lastname: Bansal
authors.affiliation: College of Engineering, Swansea University, Bay Campus, Fabian Way, Crymlyn Burrows, Swansea SA1 8EN, United Kingdom.
authors.forename: Huw D
authors.initials: HD
authors.lastname: Summers
authors.affiliation: Division of Immunology, Infection, and Inflammatory Diseases, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Diebold
authors.affiliation: Immunoregulation Laboratory, MRC Center for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037742:Nanotubes, Carbon / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000941:Antigens; D004337:Drug Carriers; D037742:Nanotubes, Carbon; C110366:OVA-8; D010446:Peptide Fragments; D013438:Sulfhydryl Compounds; D014612:Vaccines; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Carbon nanotubes; Dendritic cells; Nanomedicine; Vaccine delivery