Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen‐presenting cells (APCs; e.g., dendritic cells) or T cells are educated using immunomodulatory agents including tumor‐associated antigens and adjuvants, and manipulated to induce a cascading adaptive immune response targeting tumor cells. Mesoporous silica materials are promising candidates to improve cancer immunotherapy based on their attractive properties that include high porosity, high biocompatibility, facile surface modification, and self‐adjuvanticity. Here, the recent progress on mesoporous‐silica‐based immunotherapies based on two material forms is summarized: 1) mesoporous silica nanoparticles (MSNs), which can be internalized into APCs, and 2) micrometer‐sized mesoporous silica rods (MSRs) that can form a 3D space to recruit APCs. Subcutaneously injected MSN‐based cancer vaccines can be taken up by peripheral APCs or by APCs in lymphoid organs to educate the immune system against cancer cells. MSR cancer vaccines can recruit immune cells into the MSR scaffold to induce cancer‐specific immunity. Both vaccine systems successfully stimulate the adaptive immune response to eradicate cancer in vivo. Thus, mesoporous silica has potential value as a material platform for the treatment of cancer or infectious diseases.
For the practical use of synthetic hydrogels as artificial biological tissues, flexible electronics, and conductive membranes, achieving requirements for specific mechanical properties is one of the most prominent issues. Here, we demonstrate superstrong, superstiff, and conductive alginate hydrogels with densely interconnecting networks implemented via simple reconstructing processes, consisting of anisotropic densification of pre-gel and a subsequent ionic crosslinking with rehydration. The reconstructed hydrogel exhibits broad ranges of exceptional tensile strengths (8–57 MPa) and elastic moduli (94–1,290 MPa) depending on crosslinking ions. This hydrogel can hold sufficient cations (e.g., Li+) within its gel matrix without compromising the mechanical performance and exhibits high ionic conductivity enough to be utilized as a gel electrolyte membrane. Further, this strategy can be applied to prepare mechanically outstanding, ionic-/electrical-conductive hydrogels by incorporating conducting polymer within the hydrogel matrix. Such hydrogels are easily laminated with strong interfacial adhesion by superficial de- and re-crosslinking processes, and the resulting layered hydrogel can act as a stable gel electrolyte membrane for an aqueous supercapacitor.
Owing
to the limitations of conventional cancer therapies, cancer immunotherapy
has emerged for the prevention of cancer recurrence. To provoke adaptive
immune responses that are antigen-specific, it is important to develop
an efficient antigen delivery system that can enhance the activation
and maturation of the dendritic cells (DCs) in the human body. In
this study, we synthesize hollow mesoporous silica nanoparticles with
extra-large mesopores (H-XL-MSNs) based on a single-step synthesis
from core–shell mesoporous silica nanoparticles with a core
composed of an assembly of iron oxide nanoparticles. The hollow void
inside the mesoporous silica nanoparticles with large mesopores allows
a high loading efficiency of various model proteins of different sizes.
The H-XL-MSNs are coated with a poly(ethyleneimine) (PEI) solution
to provide an immune adjuvant and change the surface charge of the
particles for loading and slow release of a model antigen. An in vitro
study using a cancer vaccine based on the PEI-coated H-XL-MSNs with
the loading of the model antigen showed an enhanced activation of
the DCs. An in vivo study demonstrated that the resulting cancer vaccine
increased the antigen-specific cytotoxic T cells, enhanced the suppression
of tumor growth, and improved the survival rate after challenging
cancer to mice. These findings suggest that these hollow MSNs with
extra-large pores can be used as excellent antigen carriers for immunotherapy.
Atopic dermatitis (AD) is a chronic
inflammatory disease associated
with unbalanced immune responses in skin tissue. Although steroid
drugs and antihistamines are generally used to treat AD, continuous
administration causes multiple side effects. High oxidative stress
derived from reactive oxygen species (ROS) has been implicated in
the pathogenesis of AD. A high level of ROS promotes the release of
pro-inflammatory cytokines and T-cell differentiation, resulting in
the onset and deterioration of AD. Here, we report a therapeutic hydrogel
patch suppressing the high oxidative stress generated in AD lesions.
The hydrogel embedded with ROS-scavenging ceria nanoparticles leads
to the decrease of both extracellular and intracellular ROS and exhibits
cytoprotective effects in a highly oxidative condition. AD-induced
mouse model studies show enhanced therapeutic outcomes, including
a decrease in the epidermal thickness and levels of AD-associated
immunological biomarkers. These findings indicate that a ROS-scavenging
hydrogel could be a promising therapeutic hydrogel patch for treating
and managing AD.
Ex vivo manipulation of autologous antigen-presenting cells and their subsequent infusion back into the patient to dictate immune response is one of the promising strategies in cancer immunotherapy. Here, a 3D alginate scaffold embedded with reduced graphene oxide (rGO) is proposed as a vaccine delivery platform for in situ long-term activation of antigen-presenting dendritic cells (DCs). High surface area and hydrophobic surface of the rGO component of the scaffold provide high loading and a very slow release of a loaded antigen, danger signal, and/or chemoattractant from the scaffold. This approach offers long-term bioavailability of the loaded cargo inside the scaffold for manipulation of recruited DCs. After mice are subcutaneously vaccinated with the macroporous alginate graphene scaffold (MAGS) loaded with ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF), this scaffold recruits a significantly high number of DCs, which present antigenic information via major histocompatibility complex class I for a long period. Furthermore, an MAGS loaded with OVA, GM-CSF, and CpG promotes production of activated T cells and memory T cells, leading to the suppression of OVA-expressing B16 melanoma tumor growth in a prophylactic vaccination experiment. This study indicates that an MAGS can be a strong candidate for long-term programming and modulating immune cells in vivo.
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