Potential of Titanium Pins Coated with Fibroblast Growth Factor-2-Calcium Phosphate Composite Layers to Reduce the Risk of Impaired Bone-Pin Interface Strength in the External Fixation of Distal Radius Fractures.

Background: The risk of impaired bone-pin interface strength in titanium (Ti) pins coated with fibroblast growth factor (FGF)-calcium phosphate (CP) composite layers is yet to be evaluated in a clinical study. This retrospective study used Weibull plot analysis to evaluate bone-pin interface strength in Ti pins coated with FGF-CP layers for external distal radius fracture fixation. Methods: The distal radial fractures were treated with external fixation. The FGF-CP group comprised five patients (all women, aged 70.4 ± 5.9 (range: 62-77) years), and the uncoated pin group comprised ten patients (eight women and two men, aged 64.4 ± 11.7 (range: 43-83) years). The pins were removed after six weeks. The insertion and extraction peak torques were measured. The extraction peak torque was evaluated using Weibull plot analysis. Results: We compared the extraction torque of the two groups at or below 506 Nmm for a fair comparison using Weibull plot analysis. The Weibull plots were linear for both the FGF-CP and uncoated pin groups. The slope of the regression line was significantly higher in the FGF-CP group (1.7343) than in the uncoated pin group (1.5670) (p = 0.011). The intercept of the regression line was significantly lower in the FGF-CP group (-9.847) than in the uncoated pin group (-8.708) (p = 0.002). Thus, the two regression lines significantly differed. Conclusions: Ti pins coated with FGF-CP layers exhibit the potential to reduce the risk of impaired bone-pin interface strength in the external fixation of distal radius fractures.

Femtosecond Laser Irradiation to Zirconia Prior to Calcium Phosphate Coating Enhances Osteointegration of Zirconia in Rabbits.

Calcium phosphate (CaP) coating of zirconia and zirconia-based implants is challenging, due to their chemical instability and susceptibility to thermal and mechanical impacts. A 3 mol% yttrium-stabilized tetragonal zirconia polycrystal was subjected to femtosecond laser (FsL) irradiation to form micro- and submicron surface architectures, prior to CaP coating using pulsed laser deposition (PLD) and low-temperature solution processing. Untreated zirconia, CaP-coated zirconia, and FsL-irradiated and CaP-coated zirconia were implanted in proximal tibial metaphyses of male Japanese white rabbits for four weeks. Radiographical analysis, push-out test, alizarin red staining, and histomorphometric analysis demonstrated a much improved bone-bonding ability of FsL-irradiated and CaP-coated zirconia over CaP-coated zirconia without FsL irradiation and untreated zirconia. The failure strength of the FsL-irradiated and CaP-coated zirconia in the push-out test was 6.2-13.1-times higher than that of the CaP-coated zirconia without FsL irradiation and untreated zirconia. Moreover, the adhesion strength between the bone and FsL-irradiated and CaP-coated zirconia was as high as that inducing host bone fracture in the push-out tests. The increased bone-bonding ability was attributed to the micro-/submicron surface architectures that enhanced osteoblastic differentiation and mechanical interlocking, leading to improved osteointegration. FsL irradiation followed by CaP coating could be useful for improving the osteointegration of cement-less zirconia-based joints and zirconia dental implants.

Clinical Trial for the Safety and Feasibility of Pedicle Screws Coated with a Fibroblast Growth Factor-2-Apatite Composite Layer for Posterior Cervical Fusion Surgery.

To solve the instrument loosening problem, we developed a fibroblast growth factor-2-calcium phosphate composite layer as a novel coating material to improve screw fixation strength. The primary aim of the present study was to demonstrate the safety and feasibility of screws coated with the FGF-2-calcium phosphate composite layer for posterior instrumented surgery of the cervical spine. The trial design was a single-arm, open-label, safety and feasibility study. Patients receiving fusion of the cervical spine from C2 (or C3) to C7 (or T1) were recruited. The primary endpoint to confirm safety was any screw-related adverse events. Seven patients who underwent posterior fusion surgery of the cervical spine were enrolled in the present study. The coated pedicle screws were inserted bilaterally into the lowest instrumented vertebrae. There was only one severe adverse event unrelated with the coated screw. Three out of the fourteen coated screws showed loosening. The present results prove the safety and feasibility of pedicle screws coated with the FGF-2-calcium phosphate composite layer for fusion surgery in the cervical spine. This is the first step to apply this novel surface coating in the field of spine surgery.

The enhancing effects of heparin on the biological activity of FGF-2 in heparin-FGF-2-calcium phosphate composite layers.

Orthopedic and dental implants coated with fibroblast growth factor-2 (FGF-2)-calcium phosphate composite layers promote dermis formation, bone formation, and angiogenesis because of the biological activity of FGF-2. Enhancing the biological activity of FGF-2 in the composite layers is important for its wider application in orthopedics and dentistry. This study incorporated low-molecular-weight heparin (LMWH) into the FGF-2-calcium phosphate composite layers and clarified the enhancing effects of LMWH on the biological activity of FGF-2 in the composite layers in vitro. LMWH-FGF-2-calcium phosphate composite layers were successfully formed on zirconia in supersaturated calcium phosphate solutions. The composite layers comprised continuous and macroscopically homogeneous layers and particles smaller than 500 nm in size composed of amorphous calcium phosphate. The amounts of Ca and P deposited on zirconia remained almost unchanged with the addition of LMWH under the presence of FGF-2 in the supersaturated calcium phosphate solution. The LMWH in the supersaturated calcium phosphate solution increased the stability of FGF-2 in the solution and the amount of FGF-2 in the composite layers. The LMWH in the composite layers increased the mitogenic and endothelial tube-forming activities of FGF-2, and FGF-2 activity of inducing osteogenic differentiation gene expression pattern in the composite layers. Our results indicate that the enhanced biological activity of FGF-2 in the LMWH-FGF-2-calcium phosphate composite layers is attributed to an LMWH-mediated increase in the amount of FGF-2, which maintains its biological activity in the supersaturated calcium phosphate solution and the composite layers. The LMWH-FGF-2-calcium phosphate composite layer is a promising coating for orthopedic and dental implants. STATEMENT OF SIGNIFICANCE: Orthopedic and dental implants coated with fibroblast growth factor-2 (FGF-2)-calcium phosphate composite layers promote dermis formation, bone formation, and angiogenesis because of the biological activity of FGF-2. Enhancing the biological activity of FGF-2 in the layers is important for wider its application in orthopedics and dentistry. This study demonstrates the enhancing effects of low-molecular-weight heparin (LMWH) contained within LMWH-FGF-2-calcium phosphate composite layers on the biological activity of FGF-2 in vitro. Our results indicate that the enhanced biological activity of FGF-2 within the composite layers arises from an LMWH-mediated increase in the amount of FGF-2, which maintains its biological activity in the LMWH-FGF-2-calcium phosphate composite layers and supersaturated calcium phosphate solutions used for coating the composite layers.

Synergistic anti-tumor efficacy of a hollow mesoporous silica-based cancer vaccine and an immune checkpoint inhibitor at the local site.

Immune checkpoint inhibitors elicit durable tumor regression in multiple types of tumor, but may induce potential side effects with low response rates in many tumors. Herein, to increase the therapeutic efficacy of immune checkpoint inhibitors, a hollow mesoporous silica (HMS) nanosphere-based cancer vaccine was combined with an immune checkpoint inhibitor, anti-programmed death-ligand 1 (anti-PD-L1) antibody. The HMS nanospheres function as adjuvants that promote dendritic cell activation and antigen cross-presentation. Mice immunized with the HMS-based cancer vaccine show suppressed tumor growth with increased tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-2 (IL-2) levels in their spleens compared with those without HMS-based cancer vaccine. Moreover, the HMS-based cancer vaccine synergistically acts with the anti-PD-L1 antibody on the tumor. The combination of an HMS-based cancer vaccine and an antibody markedly decreases the required dose of the immune checkpoint inhibitor. Mice locally administered with the HMS-based cancer vaccine and 1/8 dose of a standard anti-PD-L1 antibody (25 µg/mouse) show comparable anti-tumor effect and significantly increased CD4+ and CD8+ T cell populations, compared with those systemically immunized with the standard anti-PD-L1 antibody done at 200 µg/mouse. Our work presents a promising cancer treatment strategy of combining an immune checkpoint inhibitor with an HMS-based cancer vaccine. STATEMENT OF SIGNIFICANCE: The clinical benefits of checkpoint blockade therapy rekindle the hope of cancer immunotherapy. However, objective response rates in checkpoint blockade therapy remain at about 10-40% owing to multiple immunosuppressive factors. To solve these problems, herein, a hollow mesoporous silica (HMS) nanosphere-based cancer vaccine was combined with an immune checkpoint inhibitor, anti-PD-L1 antibody. The HMS-based cancer vaccine synergistically acts with the anti-PD-L1 antibody on the tumor. Mice locally administered with the HMS-based cancer vaccine and 1/8 dose of a standard anti-PD-L1 antibody (25 µg/mouse) show comparable anti-tumor effect and significantly increased CD4+ and CD8+ T cell populations, compared with those systemically immunized with the standard anti-PD-L1 antibody done at 200 µg/mouse. Our work presents a promising cancer treatment strategy of combining an immune checkpoint inhibitor with an HMS-based cancer vaccine.

Novel method for selecting slices of the same cross-sectional view from digital tomosynthesis for monitoring posterior spinal instrumentation.

BACKGROUND: A method to evaluate pedicle screw loosening on digital tomosynthesis images is yet to be established owing to lack of methods for selecting slices of the same cross-sectional view. We aimed to develop an objective method for selecting slices of the same cross-sectional view on digital tomosynthesis images. METHODS: First, an objective method of pixel selection was developed by measuring the size of glass disk and titanium alloy screw on digital tomosynthesis images followed by comparison with the actual sizes. Second, a method for selecting slices of the same cross-sectional view was explored on a bone model with posterior spinal instrumentation using the screw centerline and rod curvature as indicators of the same cross section. The angle between the screw centerline and rod was calculated to verify the accuracy in obtaining the same cross-sectional view. Third, the method for selecting slices of the same cross-sectional view was applied to six patients after posterior lumbar spinal instrumentation. RESULTS: The pixel selection method enabled objective determination of a pixel on the peripheral lines of objects with an error as low as 200 µm in distance measurements on titanium alloy and glass. The mean differences of rod-screw angles between two slices were less than 1° and were not statistically significant in the bone model and patient images. CONCLUSION: A method for selecting slices of the same cross-sectional view on digital tomosynthesis images was successfully developed. This method can enable objective and quantitative evaluations of pedicle screw loosening.

Biosafety of mesoporous silica nanoparticles: a combined experimental and literature study.

Mesoporous silica (MS) particles have been explored for various healthcare applications, but universal data about their safety and/or toxicity are yet to be well-established for clinical purposes. Information about general toxicity of hollow MS (HMS) particles and about immunotoxicity of MS particles are significantly lacked. Therefore, acute toxicity and immunotoxicity of HMS particles were experimentally evaluated. A systematic and objective literature study was parallelly performed to analyze the published in vivo toxicity of MS particles. Lethal acute toxicity of MS particles is likely to arise from their physical action after intravenous and intraperitoneal administrations, and only rarely observed after subcutaneous administration. No clear relationship was identified between physicochemical properties of MS particles and lethality as well as maximum tolerated dose with some exceptions. At sub-lethal doses, MS particles tend to accumulate mainly in lung, liver, and spleen. The HMS particles showed lower inflammation-inducing ability than polyinosinic-polycytidylic acid and almost the same allergy-inducing ability as Alum. Finally, the universal lowest observed adverse effect levels were determined as 0.45, 0.81, and 4.1 mg/kg (human equivalent dose) for intravenous, intraperitoneal, and subcutaneous administration of MS particles, respectively. These results could be helpful for determining an appropriate MS particle dose in clinical study.

Total body irradiation causes a chronic decrease in antioxidant levels.

Ionizing radiation exposure may not only cause acute radiation syndrome, but also an increased risk of late effects. It has been hypothesized that induction of chronic oxidative stress mediates the late effects of ionizing radiation. However, only a few reports have analyzed changes in long-term antioxidant capacity after irradiation in vivo. Our previous study demonstrated changes in whole-blood antioxidant capacity and red blood cell (RBC) glutathione levels within 50 days after total body irradiation (TBI). In this study, seven-week-old, male, C57BL/6J mice exposed to total body irradiation by X-ray and changes in whole-blood antioxidant capacity and RBC glutathione levels at ≥ 100 days after TBI were investigated. Whole-blood antioxidant capacity was chronically decreased in the 5-Gy group. The RBC reduced glutathione (GSH) level and the GSH/oxidative glutathione (GSSG) ratio were chronically decreased after ≥ 1 Gy of TBI. Interestingly, the complete blood counts (CBC) changed less with 1-Gy exposure, suggesting that GSH and the GSH/GSSG ratio were more sensitive radiation exposure markers than whole-blood antioxidant capacity and CBC counts. It has been reported that GSH depletion is one of the triggers leading to cataracts, hypertension, and atherosclerosis, and these diseases are also known as radiation-induced late effects. The present findings further suggest that chronic antioxidant reduction may contribute to the pathogenesis of late radiation effects.

Impacts of chemically different surfaces of implants on a biological activity of fibroblast growth factor-2-apatite composite layers formed on the implants.

BACKGROUND: Implants coated with fibroblast growth factor-2 (FGF-2)-apatite composite layers were previously reported to enhance soft-tissue formation, bone formation, and angiogenesis around the implants owing to the biological activity of FGF-2. However, it is unclear whether the chemistries of the material and surface of implants have some impact on the retention of the biological activity of FGF-2 in FGF-2-apatite composite layers on them. Since magnitude of the impact should be evaluated for extensive application of the composite layer to coat various implants, following items were examined; (1) surface chemistries of six implants, (2) mitogenic activities of FGF-2 in FGF-2-apatite composite layers on the implants, and (3) improved synthesis method of the composite layer for retention of the mitogenic activity of FGF-2. HYPOTHESIS: The biological activity of FGF-2 in the composite layer is affected by the chemistries of the material and surface of implants. MATERIALS AND METHODS: Six commercial products of pins and screws having different surface chemistries were coated with FGF-2-apatite composite layers. The composite layers were quantitatively analyzed for calcium (Ca), phosphorus (P) and FGF-2, and also evaluated the mitogenic activities of FGF-2. Improvement of the synthesis method was then attempted using two pin products. RESULTS: Each commercial product had a chemically and morphologically characteristic surface. FGF-2-apatite composite layers were formed on all the commercial products. Although the Ca, P, and FGF-2 contents (4.7±0.9µg/mm, 2.2±0.4µg/mm, and 21.1±3.7ng/mm, respectively) and the Ca/P molar ratios (1.69±0.01) of the composite layers were almost the same, rate of retention of the mitogenic activity of FGF-2 in the composite layers significantly decreased on some pin products (3/12-4/12). The decrease in rate of retention of the mitogenic activity of FGF-2 was prevented by a two-step synthesis method to form a composite layer on a precoating with calcium phosphate (9/12-12/12). DISCUSSION: The chemistries of the implant surfaces had a significant impact on the retention of the mitogenic activity of FGF-2 in the composite layers formed on the implant. The two-step synthesis method was useful to retain mitogenic activity of FGF-2 regardless of the surface chemistries of the implants. The two-step synthesis method has potential to expand the applicability of FGF-2-apatite composite layers to a wider range of implants. LEVEL OF EVIDENCE: III, Case control in vitro study.

Radiation Exposure Dose Distribution of Workers Engaged in Decontamination and Related Work Following the Fukushima Nuclear Disaster.

ABSTRACT: Since the Fukushima nuclear disaster in March 2011, decontamination operations have been conducted across a wide area of Japan. The Japanese System of Registration and Management of Radiation Exposure Doses for Decontamination and Related Work, which was launched in November 2013, is administered by the Radiation Effects Association with the participation of prime contractors who perform decontamination and related work. This study aims to investigate the radiation exposure dose distribution of workers engaged in decontamination and related work, using data obtained from the above registration system. We analyzed the radiation exposure dose distributions among workers in 11 Fukushima prefectural municipalities (Futaba, Iitate, Katsurao, Kawamata, Kawauchi, Namie, Naraha, Minamisoma, Okuma, Tamura, and Tomioka) from 2013 to 2018. The mean radiation exposure doses of workers in each municipality were generally low, although a Kruskal-Wallis test showed a significant regional difference in the figures. The highest mean dose was 0.5 mSv in Okuma in 2018, and the second highest was that of Futaba. The workers engaged in the land development and construction of the interim facilities may have been exposed to more radiation than other workers across 11 Fukushima prefectural municipalities. Following large-scale nuclear accidents or radiation emergencies, radiation dose monitoring and health management for each worker need to be optimized according to their work assignments.

A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity.

Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10-40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.

An MRI-visible immunoadjuvant based on hollow Gd2O3 nanospheres for cancer immunotherapy.

Hollow Gd2O3 nanospheres significantly promote the cellular uptake of a tumor antigen by antigen presenting cells, exhibit pH-dependent alteration of the MR signal intensity and markedly enhance the antitumor immunity. Hollow Gd2O3 nanospheres are promising as magnetic resonance imaging (MRI)-visible cancer immunoadjuvants for cancer immunotherapy.

Cell attachment area of rat mesenchymal stem cells correlates with their osteogenic differentiation level on substrates without osteoconductive property.

Cell morphology is related to proliferation and differentiation. We previously reported that cell attachment area of rat mesenchymal stem cells (MSCs) is negatively correlated with their osteogenic differentiation level on osteoconductive hydroxyapatite (HAp) with various microstructures. In this study, the correlation between the cell attachment area and osteogenic differentiation level was investigated on substrates without osteoconductive property using tissue culture polystyrene (TCPS), and 3 mol% yttria-stabilized zirconia (3Y-TZP) with or without surface periodic microstructures. It was found that the osteogenic differentiation level after 3 weeks of culture increased with a decrease in cell attachment area after 3 h of culture. The square of the correlation coefficient between cell attachment area and osteocalcin secretion content was 0.845 among the three types of substrates. Thus, the negative correlation between cell attachment area and differentiation level is confirmed even when cultured on substrates without osteoconductive property. These findings suggest that the correlation between the cell attachment area of rat MSCs and osteogenic differentiation level could also apply to various types of substrate, regardless of osteoconductive property.

Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy.

Strengthening the antitumor immune response to surpass the activation energy barrier associated with the immunosuppressive tumor microenvironment is an active area of cancer immunotherapy. Emerging evidence suggests that delivery of immunostimulatory molecules with the aid of a carrier system is essential for cancer immunotherapy. However, the size-dependent effect of the delivery system on immune-targeted sites and anticancer immune responses is yet to be comprehensively understood. Herein, to clarify the size-dependent effect of the delivery system on the underlying anticancer immune mechanism, rod-shaped hydroxyapatite (HA) particles with lengths from 100 nm to 10 µm are designed. HA rods stimulate anticancer immunity in a size-dependent manner. Shorter HA rods with lengths ranging from 100 to 500 nm promote antigen cellular uptake, dendritic cell (DC) maturation, and lymph node targeting antigen. In contrast, longer HA rods with lengths ranging from 500 nm to 10 µm prolong antigen retention and increase DC accumulation. Medium-sized HA rods with a length of 500 nm, taking advantage of both short and long rods, show optimized antigen release and uptake, increased DCs accumulation and maturation, highest CD4+ and CD8+ T cell population, and the best anticancer immunity in vivo. The present study provides a rod-scale design strategy for an immune-targeted delivery system toward cancer immunotherapy in the future.

An immuno-potentiating vehicle made of mesoporous silica-zinc oxide micro-rosettes with enhanced doxorubicin loading for combined chemoimmunotherapy.

Herein, mesoporous silica-zinc oxide (MS-Zn) micro-rosettes with controllable petal thickness were synthesized by a facile one-pot hydrothermal method. MS-Zn loaded with doxorubicin and polyinosinic-polycytidylic acid sodium salt not only significantly inhibits tumor growth but also effectively rejects tumor metastasis in vivo.

Initial clinical trial of pins coated with fibroblast growth factor-2-apatite composite layer in external fixation of distal radius fractures.

BACKGROUND: Pin tract infection and loosening are major complications and challenges in the treatment of fractures by external fixation. To address this issue, we developed titanium pins coated with a fibroblast growth factor 2 (FGF-2)-apatite composite layer. The purpose of this initial clinical trial is to clarify the safety and feasibility of using these pins for the external fixation of distal radius fractures. METHODS: Unstable, displaced fractures of the distal radius that were medically suitable for external fixation were treated using external fixation pins coated and uncoated with an FGF-2-apatite composite layer. The coated pin group (n = 5) comprised 5 women (average age, 70.4 ±â€¯5.9 years), whereas the uncoated pin group (n = 10) comprised 8 women and 2 men (average age, 64.4 ±â€¯11.7 years). The average duration of external fixation was 40.8 ±â€¯1.3 and 41.6 ±â€¯2.1 days for the coated and uncoated pin groups, respectively. RESULTS: All patients achieved fracture union. One patient in the uncoated group had severe pin tract infection on the day of pin extraction. No pin loosening or difficulty in pin removal was observed in either group. Bacterial growth was present in 5% and 25% of the pin sites in the coated and uncoated groups, respectively (p = 0.059). No adverse events such as tumor formation were observed for more than 2 years after surgery in the coated pin group. CONCLUSIONS: This study clarified the safety and feasibility of using pins coated with an FGF-2-apatite composite layer for the external fixation of distal radius fractures.

Si-doping increases the adjuvant activity of hydroxyapatite nanorods.

Recombinant protein-based vaccines generally show limited immunogenicity and need adjuvants to achieve robust immune responses. Herein, to combine the excellent biocompatibility of hydroxyapatite (HA) and exciting adjuvant activity of silica, Si-doped HA nanorods with Si/P molar ratio from 0 to 0.65 were hydrothermally synthesized and evaluated as immunoadjuvants. Si-doping decreases the size and increases the BET surface area of the nanorods. Si-doping in HA nanorods increases the in vitro adjuvant activity, including CD11c+CD86+ expression and cytokine secretion of bone marrow derived dendritic cells (BMDCs). Moreover, Si-doping in HA increases the ex vivo adjuvant activity as shown by the increase in both Th1 and Th2 cytokines secretion. Si-doped HA nanorods are promising as a new immunoadjuvant.

Tailoring inorganic nanoadjuvants towards next-generation vaccines.

Vaccines, one of the most effective and powerful public health measures, have saved countless lives over the past century and still have a tremendous global impact. As an indispensable component of modern vaccines, adjuvants play a critical role in strengthening and/or shaping a specific immune response against infectious diseases as well as malignancies. The application of nanotechnology provides the possibility of precisely tailoring the building blocks of nanoadjuvants towards modern vaccines with the desired immune response. The last decade has witnessed great academic progress in inorganic nanomaterials for vaccine adjuvants in terms of nanometer-scale synthesis, structure control, and functionalization design. Inorganic adjuvants generally facilitate the delivery of antigens, allowing them to be released in a sustained manner, enhance immunogenicity, deliver antigens efficiently to specific targets, and induce a specific immune response. In particular, the recent discovery of the intrinsic immunomodulatory function of inorganic nanomaterials further allows us to shape the immune response towards the desired type and increase the efficacy of vaccines. In this article, we comprehensively review state-of-the-art research on the use of inorganic nanomaterials as vaccine adjuvants. Attention is focused on the physicochemical properties of versatile inorganic nanoadjuvants, such as composition, size, morphology, shape, hydrophobicity, and surface charge, to effectively stimulate cellular immunity, considering that the clinically used alum adjuvants can only induce strong humoral immunity. In addition, the efforts made to date to expand the application of inorganic nanoadjuvants in cancer vaccines are summarized. Finally, we discuss the future prospects and our outlook on tailoring inorganic nanoadjuvants towards next-generation vaccines.

Synergistic effects of stellated fibrous mesoporous silica and synthetic dsRNA analogues for cancer immunotherapy.

Stellated fibrous mesoporous silica nanospheres significantly improve the cellular uptake of cancer antigen and the maturation of bone marrow derived dendritic cells in vitro. Moreover, the combination of poly(I:C) with stellated fibrous MS nanospheres markedly decreases the necessary dose of poly(I:C) for anti-tumor immunity, and thus opens new opportunities for the future clinical application of poly(I:C) in cancer immunotherapy.