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Updated: May 27, 2025
Intra-lymph Node Injection of Biodegradable Polymer Particles
Published on: January 2, 2014
Topology-Oriented Lymph Node Drainage of Dendritic Polymer-TLR Agonist Conjugates to Enhance Vaccine Immunogenicity
Long Ren1, Bing Wang1, Di Miao1
1Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Breast Center, Institute of Breast Health Medicine, Sichuan Engineering Research Center for Intelligent Diagnosis and Treatment of Breast Diseases, Animal Experimental Center, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Strategically targeting lymph nodes (LNs) to orchestrate the initiation and regulation of adaptive immune responses is one of the most pressing challenges in the context of vaccination. Herein, a series of polymer-TLR agonist conjugates (PTACs) is developed to investigate the impact of dendritic-topological characteristics on their LN targeting activity in vivo, and their molecular weight (MW) on their pharmacokinetics in support of their LN homing. Notably, the dendritic 6-arm PTAC with a MW of 60 kDa (6A-PTAC-60k) rapidly delivered cargo to draining LNs after administration to peripheral tissues. Specifically, this topologic structure ameliorated the targeting behavior within lymphatic vessels and LNs, including an elevated amount of TLR7/8 agonist delivered to the LNs, an improved distribution pattern among barrier cells and immune cells, increased permeability, and prolonged retention. Furthermore, the 6A-PTAC-60k formulation induced broad antibody and T cell responses, enhancing vaccine immunogenicity and suppressing tumor growth. The results revealed that both the topology and MW of polymers are crucial factors for immunoadjuvant distribution and their functional activity in the draining LNs, which, in turn, enhanced the immunogenicity of the vaccine formulation. This study may provide a chemical and structural basis for optimizing the design of immunoadjuvant delivery systems.
Strategically targeting lymph nodes (LNs) to orchestrate the initiation and regulation of adaptive immune responses is one of the most pressing challenges in the context of vaccination. Herein, a series of polymer-TLR agonist conjugates (PTACs) is developed to investigate the impact of dendritic-topological characteristics on their LN targeting activity in vivo, and their molecular weight (MW) on their pharmacokinetics in support of their LN homing. Notably, the dendritic 6-arm PTAC with a MW of 60 kDa (6A-PTAC-60k) rapidly delivered cargo to draining LNs after administration to peripheral tissues. Specifically, this topologic structure ameliorated the targeting behavior within lymphatic vessels and LNs, including an elevated amount of TLR7/8 agonist delivered to the LNs, an improved distribution pattern among barrier cells and immune cells, increased permeability, and prolonged retention. Furthermore, the 6A-PTAC-60k formulation induced broad antibody and T cell responses, enhancing vaccine immunogenicity and suppressing tumor growth. The results revealed that both the topology and MW of polymers are crucial factors for immunoadjuvant distribution and their functional activity in the draining LNs, which, in turn, enhanced the immunogenicity of the vaccine formulation. This study may provide a chemical and structural basis for optimizing the design of immunoadjuvant delivery systems.
