Highlights from the latest research in nanomedicine.

Abstract

2015 A nanoparticulate hydrogel anticancer vaccine Evaluation of: Muraoka D, Harada N, Hayashi T et al. Nanogel-based immunologically stealth vaccine targets macrophages in the medulla of lymph node and induces potent antitumor immunity. ACS Nano 8(9), 9209–9218 (2014). Therapeutic cancer vaccines are designed to stimulate highly specific immune responses against cancers by targeting tumor-associated antigens. Various vaccines have utilized a wide range of immunogenic agents, including peptides, recombinant viruses, tumor cells and primed antigen-presenting dendritic cells, in combination with immunogenicityboosting adjuvants, immune suppression inhibitors or traditional chemotherapeutic agents [1]. However, cancer vaccines have been of varying effectiveness in clinical trials due to tumor characteristics such as antigenic heterogeneity and immunosuppressive mechanisms. Antigenic heterogeneity may allow the tumors to develop resistance against single-target immunogenic agents, while immunosuppressive mechanisms reduce the effectiveness of the immune response and alter the self-recognition mechanisms, causing cancerous cells to be ignored. Furthermore, tumor-associated antigen-targeting agents show varying immunogenic properties, with tradeoffs between specificity and effectiveness [1–3]. Nanoparticles have been of interest as efficacy-enhancing vaccine delivery agents due to their size and customizability. They are small enough to move into lymphatic systems and enter antigen-presenting cells through engulfment, and can be designed for specific parameters in terms of shape, surface properties and composition in order to enable antigen delivery specificity and presentation longevity [4,5]. Muraoka et al. developed hydrogel nanoparticles (nanogels) of approximately 50 nm in diameter using cholesteryl pullulan (CHP) polysaccharides, which self-assemble in water. These nanogels stably complex with polypeptides through hydrophobic interactions. Stability was shown for over 40 h in serum using nanogels complexed with a long-peptide antigen (LPA,) which either included the murine tumor-specific antigen mERK2 or the human tumor antigen MAGE-A4. Due to their small particle size, lack of charge and potential ligand sites, the CHP–LPA nanogel complexes travel efficiently in the lymphatic system to the draining lymph node, escaping uptake by lymph node dendritic cells until they reach the central medulla portion of the node. There, they are largely engulfed by medullary macrophages. Cellular uptake was evaluated through flow cytometry assessments of rhodamine-labeled CHP nanogels upon immune cell populations isolated from the draining lymph node. LPA that was complexed with other formulations did not show similar uptake patterns. Medullary macrophage antigen cross-presentation was assessed with CHP–mERK2 LPA, a Toll-like receptor 9 agonist and a CpG oligodeoxynucleotide adjuvant. The results showed successful T-cell recognition of mERK2-derived tumor epitopes mainly with the macrophage cells purified from the lymph nodes, with weak T-cell responses from purified dendritic cell populations. These outcomes were confirmed by impaired Highlights from the latest research in nanomedicine