In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles.
Delivery of biodegradable nanoparticles to antigen-presenting cells (APCs), specifically dendritic cells (DCs), has potential for immunotherapy. This study investigates the delivery of 20, 45, and 100nm diameter poly(ethylene glycol)-stabilized poly(propylene sulfide) (PPS) nanoparticles to DCs in the lymph nodes. These nanoparticles consist of a cross-linked rubbery core of PPS surrounded by a hydrophilic corona of poly(ethylene glycol). The PPS domain is capable of carrying hydrophobic drugs and degrades within oxidative environments. 20 nm particles were most readily taken up into lymphatics following interstitial injection, while both 20 and 45nm nanoparticles showed significant retention in lymph nodes, displaying a consistent and strong presence at 24, 72, 96 and 120h post-injection. Nanoparticles were internalized by up to 40-50% of lymph node DCs (and APCs) without the use of a targeting ligand, and the site of internalization was in the lymph nodes rather than at the injection site. Finally, an increase in nanoparticle-containing DCs (and other APCs) was seen at 96h vs. 24h, suggesting an infiltration of these cells to lymph nodes. Thus, PPS nanoparticles of 20-45nm have the potential for immunotherapeutic applications that specifically target DCs in lymph nodes.
Reddy
Sai T
ST
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL) CH-1015 Lausanne, Switzerland.
Rehor
Annemie
A
Schmoekel
Hugo G
HG
Hubbell
Jeffrey A
JA
Swartz
Melody A
MA
D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005451:Fluorescein Angiography; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013440:Sulfides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
D004337:Drug Carriers; D013440:Sulfides; C515871:poly(ethylene glycol)-stabilized poly(propylene sulfide); D011092:Polyethylene Glycols