Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard's School of Engineering and Applied Sciences (SEAS) report that a nonsurgical injection of a programmable biomaterial that spontaneously assembles in vivo into a 3D structure could fight and even help prevent cancer and also infectious disease such as HIV. Their study (“Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy”) is published in Nature Biotechnology.
“We can create 3D structures using minimally invasive delivery to enrich and activate a host's immune cells to target and attack harmful cells in vivo,” said the study's senior author David Mooney, Ph.D., who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard SEAS.
Tiny biodegradable mesoporous silica rods (MSRs) can be loaded with biological and chemical drug components and then delivered by needle just underneath the skin. The rods spontaneously assemble at the vaccination site to form a 3D scaffold, like pouring a box of matchsticks into a pile on a table. The porous spaces in the stack of MSRs are large enough to recruit and fill up with dendritic cells, which are “surveillance” cells that monitor the body and trigger an immune response when a harmful presence is detected.
“Nano-sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron-sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells,” noted co-lead author Jaeyun Kim, Ph.D., an assistant professor of chemical engineering at Sungkyunkwan University and a former Wyss Institute Postdoctoral Fellow.
Synthesized in the lab, the MSRs are built with nanopores inside. The nanopores can be filled with specific cytokines, oligonucleotides, large protein antigens, or any variety of drugs of interest to allow a vast number of possible combinations to treat a range of infections.
“Injection of an MSR-based vaccine formulation enhances systemic helper T cells TH1 and TH2 serum antibody and cytotoxic T-cell levels compared to bolus controls,” wrote the investigators. “These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.”
“Although right now we are focusing on developing a cancer vaccine, in the future we could be able to manipulate which type of dendritic cells or other types of immune cells are recruited to the 3D scaffold by using different kinds of cytokines released from the MSRs,” added co-lead author Aileen Li, a graduate student pursuing her Ph.D. in bioengineering at Harvard SEAS. “By tuning the surface properties and pore size of the MSRs, and therefore controlling the introduction and release of various proteins and drugs, we can manipulate the immune system to treat multiple diseases.”
So far, the researchers have only tested the 3D vaccine in mice, but have found that it is highly effective. An experiment showed that the injectable 3D scaffold recruited and attracted millions of dendritic cells in a host mouse, before dispersing the cells to the lymph nodes and triggering a powerful immune response.
“Injectable immunotherapies that use programmable biomaterials as a powerful vehicle to deliver targeted treatment and preventative care could help fight a whole range of deadly infections, including common worldwide killers like HIV and Ebola, as well as cancer,” pointed out Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and professor of bioengineering at Harvard SEAS. “These injectable 3D vaccines offer a minimally invasive and scalable way to deliver therapies that work by mimicking the body’s own powerful immune–response in diseases that have previously been able to skirt immune detection.”