Enhancing X-Ray Sensitization with Multifunctional Nanoparticles.

In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

Bacteria-based immunotherapy for cancer: a systematic review of preclinical studies.

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.

Coaxial electrostatic spray-based preparation of localization missile liposomes on a microfluidic chip for targeted treatment of triple-negative breast cancer.

Due to triple-negative breast cancer (TNBC) lacking specific targets for efficient therapies, nanoparticles have been widely developed to enhance efficacy and reduce the toxicity of chemotherapeutics. We prepared unique liposomes containing PTX and DOX by microfluidics-based coaxial electrostatic spray method, which have a uniform particle size, high drug loading capacity, and good stability. Meanwhile, the cRGD peptide was fused with the lipid membrane to form PTX/DOX@cRGD-Lipo, which played a GPS role in locating tumor neovascularization and further targeting TNBC cells where both overexpress αvß3. The PTX/DOX@cRGD-Lipo showed synergistic anti-tumor activity of double drugs and enhanced tumor cell apoptosis. Fluorescence microscopy and flow cytometry showed that the co-loaded targeted liposomes could be effectively absorbed by MDA-MB-231 and 4T1 cells and then released the content. In addition, the PTX/DOX@cRGD-Lipo presented excellent targeting biodistribution in vivo and a higher tumor growth inhibition rate in the orthotopic tumor mouse model. All results suggested that the double drug-loaded targeted liposome could be a promising treatment modality for TNBC.

Enhanced protection against hypoxia/reoxygenation-induced apoptosis in H9c2 cells by puerarin-loaded liposomes modified with matrix metalloproteinases-targeting peptide and triphenylphosphonium.

Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.

Knowledge mapping of syringomyelia from 2003 to 2022: A bibliometric analysis.

BACKGROUND: Syringomyelia is a chronic, progressive disease of the spinal cord. Syringomyelia is an etiologically diverse affliction caused by disturbance of normal cerebrospinal fluid flow dynamics. Lesions are characterized by the formation of tubular cavities in the gray matter of the spinal cord and gliosis; however, the etiology is unknown and treatment methods differ. Many existing studies have focused on the relationship between other diseases and syringomyelia. There is a lack of comprehensive and objective reports on the research status of syringomyelia. Therefore, this study aimed to conduct a bibliometric analysis to quantify studies on Syringomyelia and trending issues in the last 20 years. METHODS: Articles were acquired from the Web of Science Core Collection database. We used the Library Metrology online analysis platform, BICOMB, gCLUTO, CiteSpace bibliometrics tools for analysis, VOSviewer 1.6.16 (Nees Jan van Eck and Ludo Waltman, 2010), and Microsoft Excel 2019 to perform bibliometric analysis and visualization. Individual impact and collaborative information were quantified by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. We then identified the trending research areas of syringomyelia by analyzing the co-occurrence of keywords and co-cited references. RESULTS: From January 2003 to August 2022, 9,556 authors from 66 countries published a total of 1,902 research articles on syringomyelia in 518 academic journals. Most publications come from the United States, China, the United Kingdom, and Japan, with the United States dominating. Nanjing University and the University of Washington are the most active institutions, Dr. Claire Rusbridge has published the most papers, and Miholat has the most co-citations. The Journal of Neurosurgery has the highest number of co-cited articles, which are mainly in the fields of neurology, surgery, and biology. High-frequency keywords included syringomyelia, Chiari-I malformation, children, surgical treatment, and spinal cord. CONCLUSIONS: The number of articles on syringomyelia has increased steadily over the past two decades. At present, research on syringomyelia is mainly focused on the age of onset, potential therapeutic interventions, surgical treatment, avoidance of recurrence, and delay of pain. The use of surgical treatment of the disease and the mechanism of further treatment are the current hot research topics. The correlation between trauma and congenital factors, translational application, the effect of surgical treatment, postoperative recurrence, and complications are further hot research areas. These may provide ideas for further research into a radical cure for syringomyelia.

Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy.

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

Analysis of neuroendoscopy for the treatment of macroadenomas and giant pituitary adenomas.

Objective: This study investigated the use and effectiveness of endoscopic transnasal, transsphenoidal surgery, a minimally invasive method for the treatment of macroadenomas and giant pituitary a denomas, in a medical setting. The surgical results of 429 patients who received neuroendoscopic treatment of macroadenomas or giant pituitary adenomas were evaluated, and the experiences and lessons learned from treatment complications were assessed. Patients and methods: From January 2012 to December 2021, 429 patients with macroadenomas or giant pituitary adenomas, including 60 patients with giant adenomas (diameter ≥4 cm) and 369 patients with macroadenomas (diameter 1-4 cm), received a 3D head CT, a MRI with contrast enhancement, and an endocrinology examination prior to surgery. Preoperative clinical and radiological features, visual measurements, hormone levels, length of stay, length of surgery, postoperative stay, visual and hormone outcomes, resection range, complication and recurrence rates, and routine patient information were recorded. The patients were followed up for 6-72 months (median = 40 months). Results: Of 429 patients with macroadenomas or giant pituitary adenomas who received neuroendoscopic treatment, 348 (81.12%) had gross-total resections (GTR), 53 (12.35%) had near-total resections (NTR), and 28 (6.53%) had subtotal resections. There were 138 cases of post-operative diabetes insipidus (32.17%), including 7 cases of permanent diabetes insipidus (1.63%), 16 cases of nasal hemorrhage (3.73%), 39 cases of intraoperative cerebrospinal fluid leakage (9.09%), 4 cases of intracranial infection (0.9%), 16 cases of hypophysis (3.7%), and 15 cases of anosmia (3.50%). The clinical symptoms and endocrinology indices of the patients improved after surgery, and all patients were discharged 5-18 days (8.36 ± 2.65) postop. Conclusion: Neuroendoscopy is a safe operation with a short recovery period and hospital stay and is thus an effective method to treat macroadenomas and giant pituitary adenomas. Preoperative evaluation and prediction can help to accurately address possible intraoperative situations and improve GTR.

Endoscope-assisted microneurosurgery for intracranial aneurysms: A systematic review and meta-analysis.

BACKGROUND: In the surgical approach to treat deep-seated intracranial lesions, endoscopes can be used to assist microsurgical operations and improve outcomes. This technique is often called endoscope-assisted microneurosurgery (EAM). This systematic review and meta-analysis aimed to evaluate the feasibility, safety, and effectiveness of EAM. METHODS: We performed a meta-analysis of relevant articles identified using PubMed, Embase, and the Cochrane Central Register to assess the efficacy of EAM according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Primary outcomes were repositioning of the definitive clip, better surgical field, the overall and endoscope-related complication rates, mortality, and the rate of follow up. RESULTS: A total of 10 studies of 1,432 patients with 1,717 aneurysms treated with EAM were included. EAM led to repositioning of the definitive clip in 13% (95% CI, 9%-17%; I2 = 72.61%; p < 0.001); 77% of aneurysms treated with endoscopically assisted vision and information had a better outcome than that with standard surgery (95% CI, 52%-95%; I2 = 97.63%; p < 0.001). There was an overall complication rate of 6% (95% CI, 1%-13%; I2 = 91.39%; p < 0.001). The incidence of endoscope-related complications was 0% (95% CI, 0%-1%; I2 = 64%; p < 0.001). The mortality was 0% (95% CI, 0-1%; I2 = 0.0%); and 94% of patients had an excellent to good recovery and good outcome (95% CI, 88%-98%; I2 = 88.42%; p < 0.001). CONCLUSIONS: Our comprehensive study showed that EAM for intracranial aneurysms is feasible, the safety of the surgery is good, and the patients have a good prognosis, Therefore, we think EAM can be more widely adopted in the future.

An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma.

Background: Gliomas are the most common and fatal malignant type of tumor of the central nervous system. RNA post-transcriptional modifications, as a frontier and hotspot in the field of epigenetics, have attracted increased attention in recent years. Among such modifications, methylation is most abundant, and encompasses N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1 methyladenosine (m1A), and 7-methylguanosine (m7G) methylation. Methods: RNA-sequencing data from healthy tissue and low-grade glioma samples were downloaded from of The Cancer Genome Atlas database along with clinical information and mutation data from glioblastoma tumor samples. Forty-nine m6A/m5C/m1A/m7G-related genes were identified and an m6A/m5C/m1A/m7G-lncRNA signature of co-expressed long non-coding RNAs selected. Least absolute shrinkage and selection operator Cox regression analysis was used to identify 12 m6A/m5C/m1A/m7G-related lncRNAs associated with the prognostic characteristics of glioma and their correlation with immune function and drug sensitivity analyzed. Furthermore, the Chinese Glioma Genome Atlas dataset was used for model validation. Results: A total of 12 m6A/m5C/m1A/m7G-related genes (AL080276.2, AC092111.1, SOX21-AS1, DNAJC9-AS1, AC025171.1, AL356019.2, AC017104.1, AC099850.3, UNC5B-AS1, AC006064.2, AC010319.4, and AC016822.1) were used to construct a survival and prognosis model, which had good independent prediction ability for patients with glioma. Patients were divided into low and high m6A/m5C/m1A/m7G-LS groups, the latter of which had poor prognosis. In addition, the m6A/m5C/m1A/m7G-LS enabled improved interpretation of the results of enrichment analysis, as well as informing immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Conclusion: In this study we constructed an m6A/m5C/m1A/m7G-LS and established a nomogram model, which can accurately predict the prognosis of patients with glioma and provides direction toward promising immunotherapy strategies for the future.

Tizoxanide Promotes Apoptosis in Glioblastoma by Inhibiting CDK1 Activity.

The antiparasitic drug nitazoxanide (NTZ) has received considerable attention for its potential in cancer therapy. In this study, we demonstrate that tizoxanide (TIZ), an active metabolite of NTZ, exhibits antiglioma activity in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, TIZ dose-dependently inhibited the proliferation of U87, U118, and A172 human glioblastoma (GBM) cells at 48 h with IC50 values of 1.10, 2.31, and 0.73 µM, respectively. Treatment with TIZ (1 and 10 µM) also dose-dependently inhibited the colony formation of these GBM cells and accumulated ROS damage in the nucleus. In silico target fishing combined with network pharmacological disease spectrum analyses of GBM revealed that cycle-dependent kinase 1 (CDK1) is the most compatible target for TIZ and molecular docking by Molecule Operating Environment (MOE) software confirmed it. Mechanistically, TIZ inhibited the phosphorylation of CDK1 at Thr161 and decreased the activity of the CDK1/cyclin B1 complex, arresting the cell cycle at the G2/M phase. TIZ may induce apoptosis via the ROS-mediated apoptotic pathway. In vivo, TIZ suppressed the growth of established subcutaneous and intracranial orthotopic xenograft models of GBM without causing obvious side effects and prolonged the survival of nude mice bearing glioma. Taken together, our results demonstrated that TIZ might be a promising chemotherapy drug in the treatment of GBM.

Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma.

PURPOSE: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo. METHODS: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice. RESULTS: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues. CONCLUSION: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.

Recent Advance of Nanomaterial-Mediated Tumor Therapies in the Past Five Years.

Cancer has posed a major threat to human life and health with a rapidly increasing number of patients. The complexity and refractory of tumors have brought great challenges to tumor treatment. In recent years, nanomaterials and nanotechnology have attracted more attention and greatly improved the efficiency of tumor therapies and significantly prolonged the survival period, whether for traditional tumor treatment methods such as radiotherapy, or emerging methods, such as phototherapy and immunotherapy, sonodynamic therapy, chemodynamic therapy and RNA interference therapeutics. Various monotherapies have obtained positive results, while combination therapies are further proposed to prevent incomplete eradication and recurrence of tumors, strengthen tumor killing efficacy with minimal side effects. In view of the complementary promotion effects between different therapies, it is vital to utilize nanomaterials as the link between monotherapies to achieve synergistic performance. Further development of nanomaterials with efficient tumor-killing effect and better biosafety is more in line with the needs of clinical treatment. In a word, the development of nanomaterials provides a promising way for tumor treatment, and here we will review the emerging nanomaterials towards radiotherapy, phototherapy and immunotherapy, and summarized the developed nanocarriers applied for the tumor combination therapies in the past 5 years, besides, the advances of some other novel therapies such as sonodynamic therapy, chemodynamic therapy, and RNA interference therapeutics have also been mentioned.

Recent progress of macrophage vesicle-based drug delivery systems.

Nanoparticle drug delivery systems (NDDSs) are promising platforms for efficient delivery of drugs. In the past decades, many nanomedicines have received clinical approval and completed translation. With the rapid advance of nanobiotechnology, natural vectors are emerging as novel strategies to carry and delivery nanoparticles and drugs for biomedical applications. Among diverse types of cells, macrophage is of great interest for their essential roles in inflammatory and immune responses. Macrophage-derived vesicles (MVs), including exosomes, microvesicles, and those from reconstructed membranes, may inherit the chemotactic migration ability and high biocompatibility. The unique properties of MVs make them competing candidates as novel drug delivery systems for precision nanomedicine. In this review, the advantages and disadvantages of existing NDDSs and MV-based drug delivery systems (MVDDSs) were compared. Then, we summarized the potential applications of MVDDSs and discuss future perspectives. The development of MVDDS may provide avenues for the treatment of diseases involving an inflammatory process.

Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona.

Targeted drug delivery to the glioblastoma (GBM) overcoming blood-brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy.

Exosomes and biomimetic nanovesicles-mediated anti-glioblastoma therapy: A head-to-head comparison.

Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood-brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs. Here, we perform the first head-to-head comparison study of Exos and BNVs for brain tumor drug delivery. We show that BNVs derived from brain-derived endothelial cells are competent alternative nanocarrier to natural exosomes. The drug-loading capacity of Exos and BNVs are similar, but the yield of BNVs is substantially higher (500-fold) than Exos. Doxorubicin (DOX)-loaded BNVs (BNV/DOX) and DOX-loaded Exos (Exo/DOX) showed similar pharmacokinetic profiles and prolonged circulation od DOX. Despite inconsistent mechanisms, BNV/DOX can across the BBB, and exhibit suppression effects similar to Exo/DOX on the progress of glioblastoma (GBM) in zebrafish and in vivo subcutaneous and orthotopic xenografts mice models, with minimal systemic toxicity. Findings from this head-to-head comparison study indicate that autologous BNVs is a effective alternative of Exos for brain tumor nanomedicine.

Biomimetic Liposome with Surface-Bound Elastase for Enhanced Tumor Penetration and Chemo-Immumotherapy.

Dense extracellular matrix (ECM) in the tumor stroma has been a challenge for drug penetration and cytotoxic T lymphocyte (CTL) infiltration. Neutrophil elastase (NE), in surface-bound form, can destruct ECM rapidly, may be used for remodeling tumor ECM, and overcoming tumor stromal barrier. Focusing on elastosis in triple-negative breast tumor, biomimetic liposomes with chimeric cell membrane proteins (LMP) are developed and for the first time, it is demonstrated that LMP with surface-bound elastase (NE-LMP) can target and degrade ECM effectively in tumor stroma, with minimal toxicity to normal tissues. The pretreatment of NE-LMP increases the accumulation of chemotherapeutics at the tumor site and enhances antitumor effects. Also, NE-LMP facilitates CTL infiltration in tumors and exhibits enhanced chemo-immunotherapy in combination of PD-1 immune checkpoint blockade treatment in orthotopic 4T1 tumor-bearing mice, with significantly prolonged survival. Moreover, the remodeling of the tumor ECM by NE-LMP shows inhibiting effects on metastasis in the lung. Findings from this study suggest that NE-LMP holds promise for enhancing deep penetration of drug and infiltration of CTL in desmoplastic tumor by effective degrading ECM in the tumor stroma.

Nanoscale Formulations: Incorporating Curcumin into Combination Strategies for the Treatment of Lung Cancer.

Lung cancer remains the most common cancer worldwide. Although significant advances in screening have been made and early diagnosis strategies and therapeutic regimens have been developed, the overall survival rate remains bleak. Curcumin is extracted from the rhizomes of turmeric and exhibits a wide range of biological activities. In lung cancer, evidence has shown that curcumin can markedly inhibit tumor growth, invasion and metastasis, overcome resistance to therapy, and even eliminate cancer stem cells (CSCs). Herein, the underlying molecular mechanisms of curcumin were summarized by distinct biological processes. To solve the limiting factors that curtail the clinical applications of curcumin, nanoformulations encapsulating curcumin were surveyed in detail. Nanoparticles, including liposomes, micelles, carbon nanotubes (CNTs), solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions, were explored as proper carriers of curcumin. Moreover, it was firmly verified that curcumin has the ability to sensitize lung cancer cells to chemotherapeutic drugs, such as cisplatin and docetaxel, and to various targeted therapies. Regarding the advantages and drawbacks of curcumin, we concluded that combination therapy based on nanoparticles would be the optimal approach to broaden the application of curcumin in the clinic in the near future.

Construction and theoretical insights into the ESIPT fluorescent probe for imaging formaldehyde in vitro and in vivo.

We report the first ESIPT-based probe ABTB, for the highly sensitive and selective imaging of formaldehyde (FA). The various theoretical calculations have been systematically performed, and clearly unravel the lighting mechanism of the fluorescent probe for FA. Additionally, the probe was successfully applied in monitoring endogenous FA in the brain of AD mice.

Comparative evaluation of methods for isolating small extracellular vesicles derived from pancreatic cancer cells.

BACKGROUND: Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation are been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications. Here, we compared current isolation methods and performed a comparative analysis of sEVs from supernatant of cultured pancreatic cancer cells. METHODS: Ultracentrifugation, ultrafiltration and co-precipitation as concentration methods were firstly evaluated for yield, size, morphology and protein level of pellets. Then, isolate sEVs obtained by four different purification methods: size exclusion chromatography, density gradient ultracentrifugation, ultracentrifugation, and immunoaffinity capturing, were analysed and compared. RESULTS: For the concentration process, ultracentrifugation method obtained high quality and high concentration of pellets. For the purification process, immunoaffinity capturing method obtained the purest sEVs with less contaminants, while density gradient ultracentrifugation-based method obtained sEVs with the smallest size. Proteomic analysis revealed distinct protein contents of purified sEVs from different methods. CONCLUSIONS: For isolating sEVs derived from supernatant of cultured pancreatic cancer cell line, ultracentrifugation-based method is recommended for concentration of sEVs, density gradient ultracentrifugation-based method may be applied for obtaining purified sEVs with controlled size, immunoaffinity capturing may be suitable for studies requiring sEVs with high purity but may loss subtypes of sEVs without specific protein marker.