Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles.

Cancer remains a significant threat to human health. While numerous therapies have been developed to combat the disease, traditional treatments such as chemotherapy and radiotherapy are suboptimal and associated with significant side effects. Gene therapy is an emerging therapeutic approach that offers improved targeting and reduced side effects compared with traditional treatments. Using siRNA and other nucleic acid-based drugs in cancer treatment has generated significant interest among researchers. Nanocarriers, such as liposomes, can effectively deliver these agents to tumor sites. However, gene therapy alone is often insufficient to eradicate tumors, and there is a risk of recurrence. Therefore, combining gene therapy with other therapies using nanocarriers, such as phototherapy and magnetic hyperthermia therapy, can lead to synergistic therapeutic effects through different mechanisms. In this review, we summarize various ways in which gene therapy can be combined with other therapies and highlight the role of nanoplatforms in mediating these combined therapies, which would inspire novel design ideas toward combination therapies. Additionally, bottlenecks and barriers to gene therapy should be addressed in the near future to achieve better clinical efficacy.

Nanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases.

Infectious diseases, particularly life-threatening pathogens such as small pox and influenza, have substantial implications on public health and global economies. Vaccination is a key approach to combat existing and emerging pathogens. Immunological memory is an essential characteristic used to evaluate vaccine efficacy and durability and the basis for the long-term effects of vaccines in protecting against future infections; however, optimizing the potency, improving the quality, and enhancing the durability of immune responses remains challenging and a focus for research involving investigation of nanovaccine technologies. In this review, we describe how nanovaccines can address the challenges for conventional vaccines in stimulating adaptive immune memory responses to protect against reinfection. We discuss protein and nonprotein nanoparticles as useful antigen platforms, including those with highly ordered and repetitive antigen array presentation to enhance immunogenicity through cross-linking with multiple B cell receptors, and with a focus on antigen properties. In addition, we describe how nanoadjuvants can improve immune responses by providing enhanced access to lymph nodes, lymphnode targeting, germinal center retention, and long-lasting immune response generation. Nanotechnology has the advantage to facilitate vaccine induction of long-lasting immunity against infectious diseases, now and in the future.

Comprehensive treatment for ROS1-overexpressed pulmonary sarcomatoid carcinoma: A case report.

Key Clinical Message: In conclusion author highlights the tumor cell genetic testing or molecular pathological diagnosis plays a key role in the individualized treatment of PSC, which could benefit patients with advanced PSC. Abstract: An uncommon form of non-small-cell lung cancer (NSCLC) with a poor prognosis is pulmonary sarcomatoid carcinoma (PSC). Surgical resection is currently the preferred treatment, but guidelines for adjuvant chemotherapy have not yet been established, especially for the advanced stage. The development of molecular subgroups in the field of tumors may be advantageous to advanced PSC patients with the ongoing progress of genomics and immunology. A 54-year-old man presented to Xishan People's Hospital of Wuxi City with recurrent intermittent dry cough with fever for 1 month. Further examinations suggested the diagnosis of PSC occupying almost the entire right interlobar fissure area combined with malignant pleural effusion (Stage IVa). Pathological examination confirmed the diagnosis of PSC with ROS1 overexpressing via genetic testing. However, after three cycles of chemo-, antiangiogenetic- and immunochemical therapy, the lesion was localized, and pleural effusion disappeared, the patient subsequently received an operation which was performed as R0 resection. Unfortunately, the patient became deteriorated quickly followed by extensive metastatic nodules in the thoracic cavity. Although the patient continued to receive chemo- and immunochemical-therapy, it did not limit the progress of the tumor, leading to widespread metastasis, and eventually died of multiple organ failure. For PSC patients with Stage IVa, chemo-, antiangiogenetic- and immunochemical-therapy performs well in clinical efficacy, and comprehensive panel-based genetic testing may offer PSC patients a somewhat better prognosis. However, blindly implementing surgical treatment may bring harm to the patient and affect long-term survival. It's essential to know the surgical indications precisely by NSCLC guidelines.

Pre-Induced ICD Membrane-Coated Carrier-Free Nanoparticles for the Personalized Lung Cancer Immunotherapy.

Immunotherapy is a required adjuvant method in lung cancer therapy clinically. The single immune adjuvant failed to show the expected clinical therapeutic efficacy due to its rapid drug metabolism and inability to accumulate in the tumor site efficiently. Immunogenic cell death (ICD) is a new anti-tumor strategy combined with immune adjuvants. It can provide tumor-associated antigens, activate dendritic cells, and attract lymphoid T cells into the tumor microenvironment. Here doxorubicin-induced tumor membrane-coated iron (II)-cytosine-phosphate-guanine nanoparticles (DM@NPs) are shown for efficient co-delivery of tumor-associated antigens and adjuvant. Higher expression of ICD-related membrane proteins on the surface of the DM@NPs leads to the enhanced uptake of DM@NPs by dendritic cells (DCs), thereby promoting the DCs maturation and pro-inflammatory cytokines release. DM@NPs can remarkably increase the T cell infiltrations, remodel the tumor immune microenvironment and inhibit tumor progression in vivo. These findings reveal that pre-induced ICD tumor cell membrane-encapsulated nanoparticles can enhance immunotherapy responses and provide an effective biomimetic nanomaterial-based therapeutic strategy for lung cancer.

Retraction: A solid ultrasonic coupling membrane for superficial vascular ultrasonography.

Retraction of 'A solid ultrasonic coupling membrane for superficial vascular ultrasonography' by Di Sun et al., Nanoscale, 2022, 14, 3545-3553, https://doi.org/10.1039/D1NR05353A.

Graphdiyne oxide nanosheets display selective anti-leukemia efficacy against DNMT3A-mutant AML cells.

DNA methyltransferase 3 A (DNMT3A) is the most frequently mutated gene in acute myeloid leukemia (AML). Although chemotherapy agents have improved outcomes for DNMT3A-mutant AML patients, there is still no targeted therapy highlighting the need for further study of how DNMT3A mutations affect AML phenotype. Here, we demonstrate that cell adhesion-related genes are predominantly enriched in DNMT3A-mutant AML cells and identify that graphdiyne oxide (GDYO) display an anti-leukemia effect specifically against these mutated cells. Mechanistically, GDYO directly interacts with integrin ß2 (ITGB2) and c-type mannose receptor (MRC2), which facilitate the attachment and cellular uptake of GDYO. Furthermore, GDYO binds to actin and prevents actin polymerization, thus disrupting the actin cytoskeleton and eventually leading to cell apoptosis. Finally, we validate the in vivo safety and therapeutic potential of GDYO against DNMT3A-mutant AML cells. Collectively, these findings demonstrate that GDYO is an efficient and specific drug candidate against DNMT3A-mutant AML.

Pseudogene MSTO2P Interacts with miR-128-3p to Regulate Coptisine Sensitivity of Non-Small-Cell Lung Cancer (NSCLC) through TGF-ß Signaling and VEGFC.

Background: Coptisine has been widely used for treating a variety of cancer types. To date, whether pseudogene is implicated in coptisine resistance of NSCLC remains unknown. Methods: We performed MTT to assess the cell viability of A549 and Calu-1 cells. The transwell assay was used to examine the invasion of cells. TUNEL was used to determine apoptosis. Results: Our data showed that coptisine treatment suppressed cell viability and invasion of NSCLC cells while contributing to apoptosis. MiR-128-3p negatively regulated MSTO2P. miR-128-3p reverted MSTO2P knockdown-attenuated cell viability and invasion, as well as promoted cell apoptosis of A549 cells. Moreover, we identified TGF-ß signaling and VEGFC as key downstream effectors for MSTO2P and miR-128-3p in A549 cells. MiR-128-3p mimic inhibited TGF-ß pathway-associated genes (TGFBR1, Smad2, Smad5, and Smad9), whereas miR-128-3p inhibitor exerted opposite effect. MSTO2P knockdown led to attenuated expression levels of TGFBR1, Smad2, Smad5 and Smad9. VEGFC overexpression greatly rescued miR-128-3p-modulated cell viability, invasion, and apoptosis of A549 cells. Conclusion: MSTO2P plays a role in coptisine therapy of NSCLC through miR-128-3p. The findings will advance our understanding of NSCLC treatment.

MicroRNA-877-5p Inhibits Cell Progression by Targeting FOXM1 in Lung Cancer.

Background: Many researches revealed that microRNAs (miRNAs) function as potential oncogene or tumor suppressor gene. As an antioncogene, miR-877-5p was reduced in many tumors. Objective: This research aimed to explore the biological role and mechanisms of miR-877-5p, which may help patients with non-small-cell lung cancer (NSCLC) find effective therapeutic targets. Methods: The downstream targets of miR-877-5p were predicted by Bioinformatics software. RT-qPCR and western blot were employed to analyze the gene levels. The impacts of miR-877-5p and FOXM1 were assessed by cell function experiments. Results: The miR-877-5p was reduced in NSCLC. In addition to this, it also inhibited cell progression of NSCLC cells in vitro. Moreover, the upregulation of FOXM1 expression restored the inhibitory effect of enhancement of miR-877-5p. Conclusions: Taken together, miR-877-5p inhibited cell progression by directly targeting FOXM1, which may provide potential biomarkers for targeted therapy of NSCLC.

A solid ultrasonic coupling membrane for superficial vascular ultrasonography.

Superficial thrombophlebitis is one of the most significant complications of superficial vein thrombosis. Rapid imaging and mapping with high resolution is particularly important for accurate diagnosis so as to carry out treatment as soon as possible. Ultrasound imaging technology has been used extensively because of the low-cost, minimal invasiveness, and convenient application in clinical practice. And the ultrasonic couplant is an essential component in ultrasound examination. However, when imaging superficial structures, traditional liquid ultrasonic couplants often produce inadequate results. In this study, we investigate whether a hydrogel membrane can be used to improve the imaging of superficial vessels. To this end, we generated a polyacrylamide-bacterial nanocellulose hydrogel membrane (PAM-BC) that efficiently forms at 60 °C in only 10 min by redox polymerization. With PAM-BC-2.5, it was possible to acquire high resolution intravascular ultrasound images to assess superficial vessels in humans and the superficial vasculature in rats and miniature pigs using various brands of ultrasound instruments. The PAM-BCs represent a new, solid ultrasonic membrane which is suitable for diagnosing disease in superficial vessels.

Fabrication and Characterization of Prochloraz Nanoemulsion against Penicillium citrinum for the Postharvest Storage of Navel Oranges.

Nanoemulsions have become extremely popular water-insoluble pesticide delivery systems in recent years. In this study, prochloraz nanoemulsions were obtained by selecting the mixing ratio of surfactants (6:1, 3:1, 2:1, 1:1, 1:2, 1:3, and 1:6), surfactant concentration, and shearing time. The optimal formula was 10 wt % prochloraz, 6 wt % surfactant (2 wt % CO-100 + 4 wt % CO-360) dissolved in 6 wt % hydrocarbon solvent (S-100A), and deionized water replenished to 100 wt %. This formula meets the quality index standards of the Food and Agriculture Organization. Compared with oil-in-water emulsion (EW), the prochloraz nanoemulsion exhibited higher antifungal activity against Penicillium citrinum in vitro (lower LC50 of 1.17 mg L-1) and in vivo (fewer lesions). In addition, the L02 cells treated with the nanoemulsion had a higher survival rate and lower apoptosis rate at the same concentration. Results showed that the toxicity of the prochloraz nanoemulsion on L02 cells was lower than that of EW. The findings provide an important method for developing an efficient, safe, and environment-friendly nanoemulsion for postharvest fruit storage.

Application of 64-slice MSCT with ovarian vein tracking technique in identification of suture-fixed transposed ovaries.

OBJECTIVE: To explore the accuracy of 64-slice multislice computed tomography with ovarian vein tracking technique in identification of surgically transposed ovaries. METHODS: The CT and clinical data of 84 patients with ovarian transposition were retrospectively analyzed. Two radiologists completed the assessments independently. The CT data were analyzed twice. During the first assessment, transposed ovaries were identified on both sides of the lower paracolic gutters on enhanced axial CT images. The second assessment was carried out two months later. The presence or absence of transposed ovaries was identified by ovarian vein tracking technique. If the adjacent colon of the transposed ovary was not filled with contrast agents, two radiologists measured the CT values of the solid-appearing area of the transposed ovary and the wall of the adjacent colon. RESULTS: 84 patients with cervical cancer underwent ovarian transposition. There were 98 transposed ovaries and 70 non-transposed ovaries. The sensitivity, specificity and accuracy of the two assessments in identification of the ovaries were 72.4%, 98.6%, and 83.3% (first assessment), and 93.9%, 100% and 96.4% (second assessment). The sensitivity and accuracy of the two assessments were significantly different (p < 0.01). The solid-appearing area of the transposed ovaries and the wall of the adjacent colon in 33 cases showed soft tissue density. The CT values were (44.44 ±â€¯5.78) HU and (44.50 ±â€¯6.30) HU. The CT values were no significant difference (p > 0.05). CONCLUSION: Ovarian vein tracking technique can accurately identify the unmarked transposed ovaries, which is crucial in the diagnosis of abdominal/pelvic lesions.

Dual Energy CT (DECT) Monochromatic Imaging: Added Value of Adaptive Statistical Iterative Reconstructions (ASIR) in Portal Venography.

OBJECTIVE: To investigate the effect of the adaptive statistical iterative reconstructions (ASIR) on image quality in portal venography by dual energy CT (DECT) imaging. MATERIALS AND METHODS: DECT scans of 45 cirrhotic patients obtained in the portal venous phase were analyzed. Monochromatic images at 70keV were reconstructed with the following 4 ASIR percentages: 0%, 30%, 50%, and 70%. The image noise (IN) (standard deviation, SD) of portal vein (PV), the contrast-to-noise-ratio (CNR), and the subjective score for the sharpness of PV boundaries, and the diagnostic acceptability (DA) were obtained. The IN, CNR, and the subjective scores were compared among the four ASIR groups. RESULTS: The IN (in HU) of PV (10.05±3.14, 9.23±3.05, 8.44±2.95 and 7.83±2.90) decreased and CNR values of PV (8.04±3.32, 8.95±3.63, 9.80±4.12 and 10.74±4.73) increased with the increase in ASIR percentage (0%, 30%, 50%, and 70%, respectively), and were statistically different for the 4 ASIR groups (p<0.05). The subjective scores showed that the sharpness of portal vein boundaries (3.13±0.59, 2.82±0.44, 2.73±0.54 and 2.07±0.54) decreased with higher ASIR percentages (p<0.05). The subjective diagnostic acceptability was highest at 30% ASIR (p<0.05). CONCLUSIONS: 30% ASIR addition in DECT portal venography could improve the 70 keV monochromatic image quality.

Feasibility Study of Radiation Dose Reduction in Adult Female Pelvic CT Scan with Low Tube-Voltage and Adaptive Statistical Iterative Reconstruction.

OBJECTIVE: To evaluate image quality of female pelvic computed tomography (CT) scans reconstructed with the adaptive statistical iterative reconstruction (ASIR) technique combined with low tube-voltage and to explore the feasibility of its clinical application. MATERIALS AND METHODS: Ninety-four patients were divided into two groups. The study group used 100 kVp, and images were reconstructed with 30%, 50%, 70%, and 90% ASIR. The control group used 120 kVp, and images were reconstructed with 30% ASIR. The noise index was 15 for the study group and 11 for the control group. The CT values and noise levels of different tissues were measured. The contrast to noise ratio (CNR) was calculated. A subjective evaluation was carried out by two experienced radiologists. The CT dose index volume (CTDIvol) was recorded. RESULTS: A 44.7% reduction in CTDIvol was observed in the study group (8.18 ± 3.58 mGy) compared with that in the control group (14.78 ± 6.15 mGy). No significant differences were observed in the tissue noise levels and CNR values between the 70% ASIR group and the control group (p = 0.068-1.000). The subjective scores indicated that visibility of small structures, diagnostic confidence, and the overall image quality score in the 70% ASIR group was the best, and were similar to those in the control group (1.87 vs. 1.79, 1.26 vs. 1.28, and 4.53 vs. 4.57; p = 0.122-0.585). No significant difference in diagnostic accuracy was detected between the study group and the control group (42/47 vs. 43/47, p = 1.000). CONCLUSION: Low tube-voltage combined with automatic tube current modulation and 70% ASIR allowed the low CT radiation dose to be reduced by 44.7% without losing image quality on female pelvic scan.