Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components.
Directing nanoparticles to specific cell types using nonantibody-based methods is of increasing interest. Thiol-reactive nanoparticles can enhance the efficiency of cargo delivery into specific cells through interactions with cell-surface proteins. However, studies to date using this technique have been largely limited to immortalized cell lines or rodents, and the utility of this technology on primary human cells is unknown. Herein, we used RAFT polymerization to prepare pyridyl disulfide (PDS)-functionalized star polymers with a methoxy-poly(ethylene glycol) brush corona and a fluorescently labeled cross-linked core using an arm-first method. PDS star polymers were examined for their interaction with primary human blood components: six separate white blood cell subsets, as well as red blood cells and platelets. Compared with control star polymers, thiol-reactive nanoparticles displayed enhanced association with white blood cells at 37 °C, particularly the phagocytic monocyte, granulocyte, and dendritic cell subsets. Platelets associated with more PDS than control nanoparticles at both 37 °C and on ice, but they were not activated in the duration examined. Association with red blood cells was minor but still enhanced with PDS nanoparticles. Thiol-reactive nanoparticles represent a useful strategy to target primary human immune cell subsets for improved nanoparticle delivery.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, Victoria 3010, Australia.
Joshua J
http://orcid.org/0000-0001-9727-8356
JJ
Glass
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
Yang
Y
Li
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, Victoria 3010, Australia.
Robert
R
De Rose
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
Angus P R
http://orcid.org/0000-0001-5611-4515
AP
Johnston
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
Ewa I
EI
Czuba
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
Song Yang
SY
Khor
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
John F
JF
Quinn
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
Michael R
MR
Whittaker
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.|Department of Chemistry, University of Warwick , Gibbet Hill, Coventry CV4 7AL, United Kingdom.
Thomas P
http://orcid.org/0000-0003-2581-4986
TP
Davis
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, Victoria 3010, Australia.|Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University , Melbourne, Victoria 3800, Australia.
Stephen J
http://orcid.org/0000-0002-8539-4891
SJ
Kent
D006801:Humans; D053758:Nanoparticles; D011092:Polyethylene Glycols; D058105:Polymerization; D011108:Polymers; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D011108:Polymers; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols
blood; platelets; star polymers; targeting; thiols