Novel Nanotherapeutics for Cancer Immunotherapy by PD-L1-Aptamer-Functionalized and Fexofenadine-Loaded Albumin Nanoparticles.

Immune checkpoint blockade (ICB) is an important strategy for cancer treatment and has achieved remarkable clinical results. Further enhancement of the efficacy of ICB therapy with a new technical approach is of potential medical importance. In this study, we constructed a novel nanotherapeutic agent (PDL1-NP-FEXO) for cancer immunotherapy by attaching PD-L1 aptamers to albumin nanoparticles that were loaded with H1-antihitamine fexofenadine (FEXO). FEXO has been reported to enhance the immunotherapy response by reducing the immunosuppressive M2-like macrophages in the tumor microenvironment. The albumin nanoparticle was fabricated using a self-assembly method. A dynamic light scattering (DLS) study revealed that the average size of PD-L1 aptamer-modified nanoparticle without FEXO (PDL1-NP) was 135.5 nm, while that of PDL1-NP-FEXO was 154.6 nm. Similar to free PD-L1 aptamer, PDL1-NP could also bind with PD-L1-expressing tumor cells (MDA-MB-231). Of note, compared with free PD-L1 aptamer, PDL1-NP significantly boosted tumor inhibition in CT26-bearing mice. Moreover, PDL1-NP-FEXO further enhanced the antitumor efficacy vs. PDL1-NP in an animal model, without raising systemic toxicity. These results indicate that PDL1-NP-FEXO represents a promising strategy to improve ICB efficacy and may have application potential in cancer immunotherapy.

Novel nanotherapeutics for cancer immunotherapy by CTLA-4 aptamer-functionalized albumin nanoparticle loaded with antihistamine.

INTRODUCTION: Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has generated remarkable clinical results against multiple malignancies. Exploration of new technical approaches to further boost the therapeutic efficacy of ICB is of potential medical importance. In this study, we designed a novel nanotherapeutics for ICB immunotherapy. METHODS: CTLA-4 aptamers were conjugated to the surface of albumin nanoparticle to construct an aptamer-modified nanostructure (Apt-NP). To improve ICB efficacy, fexofenadine (FEXO), an antihistamine, was encapsulated into Apt-NP to make a drug-loaded nanoparticle (Apt-NP-FEXO). The antitumor efficacies of Apt-NP and Apt-NP-FEXO were evaluated in vitro and in vivo. RESULTS: Apt-NP and Apt-NP-FEXO had average diameters of 149 nm and 159 nm, respectively. Similar to free CTLA-4 aptamers, Apt-modified NPs could selectively bind with CTLA-4 positive cells and improve lymphocyte-mediated antitumor cytotoxicity in vitro. In animal studies, compared with free CTLA-4 aptamer, Apt-NP significantly enhanced antitumor immunity. Moreover, Apt-NP-FEXO further improved antitumor efficacy vs. Apt-NP in vivo. CONCLUSION: The results suggest that Apt-NP-FEXO represents a novel strategy to improve ICB outcome and may have application potential in cancer immunotherapy.

Bovine pericardium leaflet damage during transcatheter aortic valve crimping: a study of the mechanisms.

Leaflet damage has been documented to occur while deploying a transcatheter aortic valve (TAV) due to mechanical loads during the crimping procedures. In this study, the impact of compressive stress on folded leaflets was measured to investigate the mechanism of traumatic leaflet tissue damage. Numerical simulation of TAV crimping procedure was adapted to calculate stress magnitude and distribution of leaflets. A 20 mm balloon expanding short stent TAV with 0.25 mm thickness leaflets was used in the simulation. Then the calculated stresses were applied on leaflet material (bovine pericardium) samples by loading experiments. Mechanical properties evaluation combined with histological and microscopy observation were used to investigate the tissue damage. The elastic modulus and the tensile strength of the tissue began to decrease significantly at 2 MPa stress and 2.5 MPa stress, respectively. No significant differences were observed at 0-1.5 MPa stress. When the TAV was crimped to 14 Fr and 12 Fr, the 2 MPa greater areas on leaflets increased from 18.17% to 76.96%. 2 MPa compressive stress might be the threshold value for leaflet damage. The TAV crimping size should be paid attention to avoid the compressive stress higher than 2 MPa.

The Regulatory Effect of Braided Silk Fiber Skeletons with Differential Porosities on In Vivo Vascular Tissue Regeneration and Long-Term Patency.

The development of small-diameter vascular grafts that can meet the long-term patency required for implementation in clinical practice presents a key challenge to the research field. Although techniques such as the braiding of scaffolds can offer a tunable platform for fabricating vascular grafts, the effects of braided silk fiber skeletons on the porosity, remodeling, and patency in vivo have not been thoroughly investigated. Here, we used finite element analysis of simulated deformation and compliance to design vascular grafts comprised of braided silk fiber skeletons with three different degrees of porosity. Following the synthesis of low-, medium-, and high-porosity silk fiber skeletons, we coated them with hemocompatible sulfated silk fibroin sponges and then evaluated the mechanical and biological functions of the resultant silk tubes with different porosities. Our data showed that high-porosity grafts exhibited higher elastic moduli and compliance but lower suture retention strength, which contrasted with low-porosity grafts. Medium-porosity grafts offered a favorable balance of mechanical properties. Short-term in vivo implantation in rats indicated that porosity served as an effective means to regulate blood leakage, cell infiltration, and neointima formation. High-porosity grafts were susceptible to blood leakage, while low-porosity grafts hindered graft cellularization and tended to induce intimal hyperplasia. Medium-porosity grafts closely mimicked the biomechanical behaviors of native blood vessels and facilitated vascular smooth muscle layer regeneration and polarization of infiltrated macrophages to the M2 phenotype. Due to their superior performance and lack of occlusion, the medium-porosity vascular grafts were evaluated in long-term (24-months) in vivo implantation. The medium-porosity grafts regenerated the vascular smooth muscle cell layers and collagen extracellular matrix, which were circumferentially aligned and resembled the native artery. Furthermore, the formed neoarteries pulsed synchronously with the adjacent native artery and demonstrated contractile function. Overall, our study underscores the importance of braided silk fiber skeleton porosity on long-term vascular graft performance and will help to guide the design of next-generation vascular grafts.

Novel Complex of PD-L1 Aptamer and Albumin Enhances Antitumor Efficacy In Vivo.

The PD-1/PD-L1 pathway blockade can generate a good clinical response by reducing immunosuppression and provoking durable antitumor immunity. In addition to antibodies, aptamers can also block the interaction between PD-1 and PD-L1. For the in vivo application, however, free aptamers are usually too small in size and quickly removed from blood via glomerular filtration. To avoid renal clearance of aptamer, we conjugated the PD-L1 aptamer to albumin to form a larger complex (BSA-Apt) and evaluated whether BSA-Apt would enhance the in vivo antitumor efficacy. The PD-L1 aptamer was thiol-modified and conjugated to the amino group of BSA via a SMCC linker. The average size of BSA-Apt was 11.65 nm, which was above the threshold for renal clearance. Functionally, BSA-Apt retained the capability of the PD-L1 aptamer to bind with PDL1-expressing tumor cells. Moreover, both the free aptamer and BSA-Apt augmented the PBMC-induced antitumor cytotoxicity in vitro. Furthermore, BSA-Apt generated a significantly stronger antitumor efficacy than the free PD-L1 aptamer in vivo without raising systemic toxicity. The results indicate that conjugating the PD-L1 aptamer to albumin may serve as a promising strategy to improve the in vivo functionality of the aptamer and that BSA-Apt may have application potential in cancer immunotherapy.

The differences between surface degradation and bulk degradation of FEM on the prediction of the degradation time for poly (lactic-co-glycolic acid) stent.

The degradation time is a crucial factor in evaluating the performance of poly (lactic-co-glycolic acid) (PLGA) stents. Bulk degradation mode was commonly used to analyze the stent degradation behavior by finite element approach. However, the PLGA stents may present surface degradation more than bulk degradation under certain conditions, which will greatly affect the degradation time after implantation. In this study, the degradation processes of the poly (lactic-co-glycolic acid) stent were reproduced utilizing finite element analysis. Both bulk degradation and surface degradation modes were considered. The correlation between tensile stress and degradation rate was investigated. The degradation time was analyzed selectively. The stress distribution, fracture, and mass loss were also compared between bulk degradation mode and surface degradation mode. The simulation results showed that, in both evolution modes, the degradation began at the 'peak-valley' region and fracture occurred at the cross of links and rings. Additionally, high levels of Von-Mises stress were observed in these two regions. Compared with bulk degradation, the fracture time of the stent was delayed by 63% in the surface degradation mode. In conclusion, the mass loss rate and scaffolding period showed great differences between surface degradation and bulk degradation. Based on this study, it is suggested that bulk degradation mode is not applicable to the case of inadequate water uptake mode, such as the tracheal stent degradation process. More experimental research should be carried out to accurately predict the scaffolding period after implantation. The mechanical properties of the fracture zone should be strengthened.

Investigation of failure modes of explanted porcine valves in the mitral position.

BACKGROUND: Porcine valves are used for mitral valve replacement, but the limited long-term durability has restricted the application in younger patients. Degenerated porcine mitral valves were explanted to analyze the failure modes and damage characteristics. METHODS: Twelve porcine valves were explanted via secondary mitral valve replacement surgery. Microcomputed tomography scanning, morphological and pathological examinations were performed to classify the cusp tears, calcification, and pannus formation. The causes of valve deterioration were subsequently analyzed. RESULTS: The mean age at first implantation was 45.42±19.58 years (range, 11-64 years). The mean duration of implantation was 9.39±4.14 years (range, 4.25-18.75 years). The indications for first surgery were rheumatic heart disease in 8 patients (66.67%), infective endocarditis in 2 patients (16.67%), degenerative valvular disease in one patient (8.33%), and congenital heart disease in one patient (8.33%). Type I cusp tears and commissural dehiscence that occurred near the stent post position were found in 6 (50%) and 5 (41.67%) valves, respectively. Calcification was detected in 6 (50%) cases, and pannus was found in most valves (91.67%). CONCLUSIONS: Leaflet damage occurred near the stent posts area was the main failure mode of porcine mitral valves in this study. Patients who undergo the first surgery at younger age, the higher prevalence rate of rheumatic heart disease, the structure of bioprosthetic porcine valve, and left ventricular stresses could be considered as the main factors causing valve deterioration.

Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo.

Blocking the PD-1/PD-L1 pathway can diminish immunosuppression and enhance anticancer immunity. PD-1/PD-L1 blockade can be realized by aptamers, which have good biocompatibility and can be synthesized in quantity economically. For in vivo applications, aptamers need to evade renal clearance and nuclease digestion. Here we investigated whether DNA nanostructures could be used to enhance the function of PD-L1 aptamers. Four PD-L1 aptamers (Apt) were built into a Holliday Junction (HJ) to form a tetravalent DNA nanostructure (Apt-HJ). The average size of Apt-HJ was 13.22 nm, which was above the threshold for renal clearance. Apt-HJ also underwent partial phosphorothioate modification and had improved nuclease resistance. Compared with the monovalent PD-L1 aptamer, the tetravalent Apt-HJ had stronger affinity to CT26 colon cancer cells. Moreover, Apt-HJ markedly boosted the antitumor efficacy in vivo vs. free PD-L1 aptamers without raising systemic toxicity. The results indicate that multiple aptamers attached to a DNA nanostructure may significantly improve the function of PD-L1 aptamers in vivo.

Excretion of SARS-CoV-2 through faecal specimens.

Coronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT-PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.

Targeted Treatment of Colon Cancer with Aptamer-Guided Albumin Nanoparticles Loaded with Docetaxel.

PURPOSE: Chemotherapy of colon cancer needs improvement to mitigate the severe adverse effects (AEs) associated with the cytotoxic drugs. The aim of this study is to develop a novel targeted drug delivery system (TDDS) with practical application potential for colon cancer treatment. METHODS: The TDDS was built by loading docetaxel (DTX) in albumin nanoparticles (NPs) that were functionalized with nucleolin-targeted aptamers (AS1411). RESULTS: The TDDS (Apt-NPs-DTX) had an average size of 62 nm and was negatively charged with a zeta potential of -31.2 mV. DTX was released from the albumin NP with a typical sustained release profile. Aptamer-guided NPs were preferentially ingested by nucleolin-expressing CT26 colon cancer cells vs the control cells. In vitro cytotoxicity study showed that Apt-NPs-DTX significantly enhanced the killing of CT26 colon cancer cells. Importantly, compared with non-targeted drug delivery, Apt-NPs-DTX treatment significantly improved antitumor efficacy and prolonged the survival of CT26-bearing mice, without raising systemic toxicity. CONCLUSION: The results suggest that Apt-NPs-DTX has potential in the targeted treatment of colon cancer.

Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin.

PURPOSE: Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells. METHODS: The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox. RESULTS: Apt-HJ had an average size of 12.45 nm and a zeta potential of -11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects. CONCLUSION: These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.

Influence of Configuration on Stress Distribution of Pulmonary Monocusp Leaflet.

PURPOSE: For the relief of right ventricular outflow tract obstruction in operative treatment of tetralogy of Fallot and other complex congenital heart diseases, transannular monocusp patch operations are often necessary to prevent right ventricular pressure overload and reduce pulmonary regurgitation. However, long-term durability of a monocusp leaflet is unsatisfactory, its failure is believed to be related to mechanical stress, whose distribution is primarily affected by geometric configurations. Therefore, the influence of several geometrical parameters on stress distribution of leaflet is investigated. METHODS: Five parameters affecting leaflet configuration were established: angle between free edge of the leaflet and vessel wall, angle formed by the two end points of free edge, length of the free edge of the leaflet, height of the leaflet, and shape of elliptic conical surface constituting the leaflet surface. The first four parameters were fixed, and two factors were defined to describe the last parameter. Seven models with different values of these factors were analyzed using finite element method at the pressure of the pulmonary artery loaded on the leaflet. RESULTS: The peak stresses of all models occurred at end points of the free edge of the leaflet (tear high-risk regions). The middle of leaflet had the greatest stress gradient and produced tissue wrinkling; this area could be the risk region of calcification. Both factors were noted to influence the stress distribution, and one of the factors could also relieve the wrinkling. CONCLUSIONS: The leaflet of model (1.2_min) had the most even stress distribution and lowest peak principal stress, which was the optimal choice among all the models.

Selection of a novel DNA aptamer against OFA/iLRP for targeted delivery of doxorubicin to AML cells.

The standard treatment for most acute myeloid leukemia (AML) is chemotherapy, which is often associated with severe adverse effects. One strategy to reduce the adverse effects is targeted therapy that can selectively deliver anticancer drugs to tumor cells. Immature laminin receptor protein (OFA/iLRP) is a potential target for AML treatment, because it is over-expressed on the surface of AML cells but under-expressed in normal tissue. In this study, we developed the first aptamer for OFA/iLRP and explored its potential as a targeting ligand for delivery of doxorubicin (Dox) to AML cells in vitro. The selected aptamer (AB3) was a 59-base DNA oligonucleotides. It bound to OFA/iLRP structure with a Kd of 101 nM and had minimal cross-reactivity to albumin, trypsin, or ovalbumin. Moreover, AB3 could bind to OFA/iLRP-positive AML cells but not the OFA/iLRP-negative control cells. An aptamer-doxorubicin (Apt-Dox) complex was formed by intercalating doxorubicin into the DNA structure of AB3. Apt-Dox selectively delivered Dox to OFA/iLRP-positive AML cells but notably decreased the drug intake by OFA/iLRP-negative control cells. In addition, cytotoxicity study revealed that Apt-Dox efficaciously destroyed the OFA/iLRP-positive AML cells, but significantly reduced the damage to control cells. The results indicate that the OFA/iLRP aptamer AB3 may have application potential in targeted therapy against AML.

HIV prevalence in suspected Ebola cases during the 2014-2016 Ebola epidemic in Sierra Leone.

BACKGROUND: The 2014-2016 Ebola virus epidemic in West Africa was the largest outbreak of Ebola virus disease (EVD) in history. Clarifying the influence of other prevalent diseases such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) will help improve treatment and supportive care of patients with EVD. CASE PRESENTATION: We examined HIV and hepatitis C virus (HCV) antibody prevalence among suspected EVD cases from the Sierra Leone-China Friendship Biological Safety Laboratory during the epidemic in Sierra Leone. HIV and HCV antibodies were tested in 678 EVD-negative samples by enzyme-linked immunosorbent assay. A high HIV prevalence (17.6%) and low HCV prevalence (0.22%) were observed among the suspected cases. Notably, we found decreased HIV positive rates among the suspected cases over the course of the epidemic. This suggests a potentially beneficial effect of an improved public health system after assistance from the World Health Organization and other international aid organizations. CONCLUSIONS: This EVD epidemic had a considerable impact on the public health system and influenced the prevalence of HIV found among suspected cases in Sierra Leone, but also provided an opportunity to establish a better surveillance network for infectious diseases.

Novel Bispecific Aptamer Enhances Immune Cytotoxicity Against MUC1-Positive Tumor Cells by MUC1-CD16 Dual Targeting.

A promising strategy in cancer immunotherapy is the employment of a bispecific agent that can bind with both tumor markers and immunocytes for recruitment of lymphocytes to tumor sites and enhancement of anticancer immune reactions. Mucin1 (MUC1) is a tumor marker overexpressed in almost all adenocarcinomas, making it a potentially important therapeutic target. CD16 is expressed in several types of immunocytes, including NK cells, γδ-T cells, monocytes, and macrophages. In this study, we constructed the first bispecific aptamer (BBiApt) targeting both MUC1 and CD16. This aptamer consisted of two MUC1 aptamers and two CD16 aptamers linked together by three 60 nt DNA spacers. Compared with monovalent MUC1 or CD16 aptamers, BBiApt showed more potent avidity to both MUC1-positive tumor cells and CD16-positive immunocytes. Competition experiments indicated that BBiApt and monovalent aptamers bound to the same sites on the target cells. Moreover, BBiApt recruited more CD16-positive immunocytes around MUC1-positive tumor cells and enhanced the immune cytotoxicity against the tumor cells in vitro. The results suggest that, apart from bispecific antibodies, bispecific aptamers may also potentially serve as a novel strategy for targeted enhancement of antitumor immune reactions against MUC1-expressing malignancies.

Serological Investigation of Laboratory-Confirmed and Suspected Ebola Virus Disease Patients During the Late Phase of the Ebola Outbreak in Sierra Leone.

This study aimed to investigate the serological characteristics of Ebola virus (EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease (EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction (RT-PCR) for viral RNA and enzyme-linked immunosorbent assay (ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1% (18/31) and 93.5% (29/31) of the confirmed EVD patients and in 3.8% (25/663) and 17.8% (118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection. The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.

Selection of a novel CD19 aptamer for targeted delivery of doxorubicin to lymphoma cells.

CD19 is overexpressed in most human B cell malignancies and considered an important tumor marker for diagnosis and treatment. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand for targeted cancer therapy with excellent affinity and specificity. In this study, we selected a novel CD19 aptamer (LC1) that was a 59-nucleotide single strand DNA. The aptamer could bind to recombinant CD19 protein with a Kd of 85.4 nM, and had minimal cross reactivity to bovine serum albumin (BSA) or ovalbumin (OVA). Moreover, the aptamer was found capable of binding with the CD19-positive lymphoma cells (Ramos and Raji), but not the CD19-negative cell lines (Jurkat and NB4). An aptamer-doxorubicin complex (Apt-Dox) was also formulated, and selectively delivered doxorubicin to CD19-positive lymphoma cells in vitro. The results indicate that aptamer LC1 can recognize CD19-positive tumor cells and may potentially function as a CD19-targeting ligand.

An In Vitro Feasibility Study of the Influence of Configurations and Leaflet Thickness on the Hydrodynamics of Deformed Transcatheter Aortic Valve.

Clinically, the percutaneous transcatheter aortic valve (TAV) has been reported to be deformed in a noncircular configuration after its implant. The deformation is universal and various, and it leads to serious leakage and durability problems. Even in the same deformation, the leaflets made in different tissue thicknesses may cause different hydrodynamic performances. Simulating the left heart cardiac conditions by a pulse duplicator system, the present study investigated the effects of the aortic annulus deformation and the leaflet tissue thickness on the hydrodynamics of the TAV. Three 22 mm self-expanding TAV samples were fabricated with three different leaflet thicknesses (0.25, 0.4, 0.55 mm). Every sample was successively deformed to be elliptical, triangular, and undersized circular shapes. The hydrodynamics of the TAV were assessed through a quasi-physiological artery pulsatile flow duplicator system. The transvalvular pressure difference, effective orifice area, and regurgitation flow were determined. High-speed video recordings were taken to investigate the leaflet kinematics. The results showed that the triangular deformation produced the poorest valve function while the elliptical deformation led to the slightest difference from the nominal. With increasing leaflet thickness, the effect of configuration deformation on the regurgitation increased. The thinner leaflets were better than the thicker ones in adapting to the deformation but had a higher risk of deterioration.

Combined use of iterative reconstruction and monochromatic imaging in spinal fusion CT images.

BACKGROUND: Spinal fusion surgery is an important procedure for treating spinal diseases and computed tomography (CT) is a critical tool for postoperative evaluation. However, CT image quality is considerably impaired by metal artifacts and image noise. PURPOSE: To explore whether metal artifacts and image noise can be reduced by combining two technologies, adaptive statistical iterative reconstruction (ASIR) and monochromatic imaging generated by gemstone spectral imaging (GSI) dual-energy CT. MATERIAL AND METHODS: A total of 51 patients with 318 spinal pedicle screws were prospectively scanned by dual-energy CT using fast kV-switching GSI between 80 and 140 kVp. Monochromatic GSI images at 110 keV were reconstructed either without or with various levels of ASIR (30%, 50%, 70%, and 100%). The quality of five sets of images was objectively and subjectively assessed. RESULTS: With objective image quality assessment, metal artifacts decreased when increasing levels of ASIR were applied (P < 0.001). Moreover, adding ASIR to GSI also decreased image noise (P < 0.001) and improved the signal-to-noise ratio (P < 0.001). The subjective image quality analysis showed good inter-reader concordance, with intra-class correlation coefficients between 0.89 and 0.99. The visualization of peri-implant soft tissue was improved at higher ASIR levels (P < 0.001). CONCLUSION: Combined use of ASIR and GSI decreased image noise and improved image quality in post-spinal fusion CT scans. Optimal results were achieved with ASIR levels ≥70%.

Enhancement of Thermal Damage to Adenocarcinoma Cells by Iron Nanoparticles Modified with MUC1 Aptamer.

Hyperthermia cancer treatment is an adjunctive therapy that aims at killing the tumor cells with excessive heat that is usually generated by metal contrasts exposed to alternating magnetic field. The efficacy of hyperthermia is often limited by the heat damage to normal tissue due to indiscriminate distribution of the metal contrasts within the body. Tumor-targeting metal contrasts may reduce the toxicity of hyperthermia and improve the efficacy of thermotherapy against cancer. MUC1 is a glycoprotein over expressed in most adenocarcinomas, and represents an attractive therapeutic target. In this study, a MUC1 aptamer is conjugated with iron nanoparticles to construct adenocarcinoma-targeting metal contrasts. DNA hybridization studies confirmed that the aptamers were conjugated to the iron nanoparticles. Importantly, more aptamer-modified nanoparticles attached to the MUC1-positive cancer cells compared with the unmodified nanoparticles. Moreover, aptamer-modified nanoparticles significantly enhanced the targeted hyperthermia damage to MUC1-positive cancer cells in vitro (p < 0.05). The results suggest that MUC1 aptamer-modified metal particles may have potential in development of targeted hyperthermia therapy against adenocarcinomas.