Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

Studies on the influence of nanoparticle size on lymph node targeting began in the 1980s as scientists aimed to maximize lymphatic delivery of drugs for treating metastatic cancer. It was generally observed that following subcutaneous injections liposomes smaller than 150 nm were able to enter the lymphatic capillaries whereas larger liposomes remained at the injection sites [148] [149] [150] . In a study by Oussoren et al. using isotope labelled liposomes between 40 to 400 nm in diameter in lymphatic tracking, lymphatic uptake was found to be inversely proportional to the liposome size. 40 nm, 70 nm, 170 nm and 400 nm liposomes had approximately 76%, 61%, 30%, and 18% of the injected dose entering the lymphatic system, respectively. Curiously, despite higher lymphatic entry by smaller liposomes in the study, liposome accumulation in the draining lymph node was similar across the differently sized formulations. It was found that the majority of the small liposomes, which consisted of egg-phosphatidylcholine and egg-phosphatidylglycerol, passed through the lymph node and were ultimately captured by the liver and the spleen [151] . The result highlighted the dynamic relationship between particle size and lymph node accumulation; as smaller particles are more likely to enter the lymphatic system, they are also more likely to evade the filtering mechanism of lymph nodes. The authors showed that incorporating phosphotidylserine, a lipid more susceptible to macrophage recognition and capture, increased the lymph node accumulation by 3-fold. Other lipid modification strategies, such as steric stabilization and ligand functionalization, have also been reported to influence the lymph node accumulation of liposomes following lymphatic uptake [152] .