Remodeling of Mitochondrial Metabolism by a Mitochondria-Targeted RNAi Nanoplatform for Effective Cancer Therapy.

Emerging evidence has demonstrated the significant contribution of mitochondrial metabolism dysfunction to promote cancer development and progression. Aberrant expression of mitochondrial genome (mtDNA)-encoded proteins widely involves mitochondrial metabolism dysfunction, and targeted regulation of their expression can be an effective strategy for cancer therapy, which however is challenged due to the protection by the mitochondrial double membrane. Herein, a mitochondria-targeted RNAi nanoparticle (NP) platform for effective regulation of mitochondrial metabolism and breast cancer (BCa) therapy is developed. This nanoplatform is composed of a hydrophilic polyethylene glycol (PEG) shell, a hydrophobic poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) core, and charged-mediated complexes of mitochondria-targeting and membrane-penetrating peptide amphiphile (MMPA) and small interfering RNA (siRNA) embedded in the core. After tumor accumulation and internalization by tumor cells, these NPs can respond to the endosomal pH to expose the MMPA/siRNA complexes, which can specifically transport siRNA into the mitochondria to down-regulate mtDNA-encoded protein expression (e.g., ATP6 and CYB). More importantly, because ATP6 down-regulation can suppress ATP production and enhance reactive oxygen species (ROS) generation to induce mitochondrial damage and mtDNA leakage into tumor tissues, the NPs can combinatorially inhibit tumor growth via suppressing ATP production and repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like macrophages by mtDNA.

CARBON DOTS: Bioimaging and Anticancer Drug Delivery.

Cancer, responsible for approximately 10 million lives annually, urgently requires innovative treatments, as well as solutions to mitigate the limitations of traditional chemotherapy, such as long-term adverse side effects and multidrug resistance. This review focuses on Carbon Dots (CDs), an emergent class of nanoparticles (NPs) with remarkable physicochemical and biological properties, and their burgeoning applications in bioimaging and as nanocarriers in drug delivery systems for cancer treatment. The review initiates with an overview of NPs as nanocarriers, followed by an in-depth look into the biological barriers that could affect their distribution, from barriers to administration, to intracellular trafficking. It further explores CDs' synthesis, including both bottom-up and top-down approaches, and their notable biocompatibility, supported by a selection of in vitro, in vivo, and ex vivo studies. Special attention is given to CDs' role in bioimaging, highlighting their optical properties. The discussion extends to their emerging significance as drug carriers, particularly in the delivery of doxorubicin and other anticancer agents, underscoring recent advancements and challenges in this field. Finally, we showcase examples of other promising bioapplications of CDs, emergent owing to the NPs flexible design. As research on CDs evolves, we envisage key challenges, as well as the potential of CD-based systems in bioimaging and cancer therapy.

Decoding antimicrobial resistance: unraveling molecular mechanisms and targeted strategies.

Antimicrobial resistance poses a significant global health threat, necessitating innovative approaches for combatting it. This review explores various mechanisms of antimicrobial resistance observed in various strains of bacteria. We examine various strategies, including antimicrobial peptides (AMPs), novel antimicrobial materials, drug delivery systems, vaccines, antibody therapies, and non-traditional antibiotic treatments. Through a comprehensive literature review, the efficacy and challenges of these strategies are evaluated. Findings reveal the potential of AMPs in combating resistance due to their unique mechanisms and lower propensity for resistance development. Additionally, novel drug delivery systems, such as nanoparticles, show promise in enhancing antibiotic efficacy and overcoming resistance mechanisms. Vaccines and antibody therapies offer preventive measures, although challenges exist in their development. Non-traditional antibiotic treatments, including CRISPR-Cas systems, present alternative approaches to combat resistance. Overall, this review underscores the importance of multifaceted strategies and coordinated global efforts to address antimicrobial resistance effectively.

Influences of TiO2 nanoparticle and fipronil co-exposure on metabolite profiles in mouse intestines.

Food contaminates, such as insecticide, may influence the toxicity of nanoparticles (NPs) to intestine. The present study investigated the combined toxicity of TiO2 NPs and fipronil to male mouse intestine. Juvenile mice (8 weeks) were orally exposed to 5.74 mg/kg TiO2 NPs, 2.5 mg/kg fipronil, or both, once a day, for 5 days. We found that both TiO2 NPs and fipronil induced some pathological changes in intestines, accompanying with defective autophagy, but these effects were not obviously enhanced after TiO2 NP and fipronil co-exposure. Fipronil promoted Ti accumulation but induced minimal impact on other trace elements in TiO2 NP-exposed intestines. Metabolomics data revealed that the exposure altered metabolite profiles in mouse intestines, and two KEGG pathways, namely, ascorbate and aldarate metabolism (mmu00053) and glutathione metabolism (mmu00480), were only statistically significantly changed after TiO2 NP and fipronil co-exposure. Five metabolites, including 2-deoxy-D-erythro-pentofuranose 5-phosphate, 5alpha-cholestanol, beta-D-glucopyranuronic acid, elaidic acid, and isopentadecanoic acid, and maltotriose, were more significantly up-regulated after the co-exposure, whereas trisaccharide and xylonolactone were only significantly down-regulated by the co-exposure. We concluded that fipronil had minimal impact to enhance the toxicity of TiO2 NPs to mouse intestines but altered metabolite profiles.

Effect of CeO2, TiO2 and SiO2 nanoparticles on the growth and quality of model medicinal plant Salvia miltiorrhiza by acting on soil microenvironment.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Plasmon-Driven Photochemical Reduction Reaction on Silver Nanostructures for Green Fabrication of Superhydrophobic Surface.

Green fabrication of superhydrophobic surface by water-based processing is still challenging, because introduction of the substances with hydrophilic moieties compromises its superhydrophobicity. Herein, a plasmon-driven photochemical reduction reaction under ultraviolet light (UVA) irradiation is first discovered and is applied to deoxygenation of hydrophilic organic adsorbates on rough nano-Ag coating for the formation of stable superhydrophobic surface. A nano-Ag coating with strong localized surface plasmon resonance in the UVA region is prepared by a water-based silver mirror reaction and results in a unique chemical reduction reaction on its surface. Consequently, the low residual hydrophilic functionalities and the formed cross-linked structure of the adsorbate on Ag nanoparticles (NPs) enables the coating to exhibit stable superhydrophobicity against to both air and water. The superhydrophobic Ag NP-coated sandpaper can also be used as a surface-enhanced Raman scattering (SERS) substrate to concentrate aqueous analytes for trace detection.

Ionic-Liquid-Based Nanofluids and Their Heat-Transfer Applications: A Comprehensive Review.

Due to the improved thermophysical characteristics of ionic liquids (ILs), such as their strong ionic conductivity, negligible vapor pressure, and thermal stability at high temperatures, they are being looked at viable contender for future heat transfer fluids. Additionally, the dispersing nanoparticles can further improve the thermophysical characteristics and thermal performance of ionic liquids, which is one of the emerging research interests to increase the heat transfer rates of the thermal devices. The latest investigations about the utilization of ionic liquid nanofluids as a heat transfer fluid is summarized in this work. These summaries are broken down into three types: (a) the thermophysical parameters including thermal conductivity, viscosity, density, and specific heat of ionic liquids (base fluids), (b) the thermophysical properties like thermal conductivity, viscosity, density, and viscosity of ionic liquids based nanofluids (IL nanofluids), and (iii) utilization of IL nanofluids as a heat transfer fluid in the thermal devices. The techniques for measuring the thermophysical characteristics and the synthesis of IL nanofluids are also covered. The suggestions for potential future research directions for IL nanofluids are summarized.

Ultrafast excited-state energy dissipation pathway of diethylamino hydroxybenzoyl hexyl benzoate (DHHB) via the nanoparticles.

The organic UVA filter is popularized in sunscreen cosmetics due to the advantages of excellent light stability and high molar extinction coefficient. However, the poor water solubility of organic UV filters has been a common problem. Given that nanoparticles (NPs) can significantly improve the water solubility of organic chemicals. Meanwhile, the excited-state relaxation pathways of NPs might differ from their solution. Here, the NPs of diethylamino hydroxybenzoyl hexyl benzoate (DHHB), a popular organic UVA filter, were prepared by an advanced ultrasonic micro-flow reactor. The surfactant (sodium dodecyl sulfate) was selected as an effective stabilizer to prevent the self-aggregation of the NPs for DHHB. Femtosecond transient ultrafast spectroscopy (fs-TA) and theoretical calculations were utilized to trace and explain the excited-state evolution of DHHB in NPs suspension and its solution. The results reveal that the surfactant-stabilized NPs of DHHB reserve a similarly good performance of ultrafast excited-state relaxation. The stability characterization experiments demonstrate that the strategy of surfactant-stabilized NPs for sunscreen chemicals can maintain its stability and enhance the water solubility of DHHB compared with that of the solution phase. Therefore, the surfactant-stabilized NPs of organic UV filters are an effective method to improve water solubility and keep the stability from aggregation and photoexcitation.

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy.

Although the neurotoxicity of ZnO nanoparticles (NPs) has been evaluated in animal and nerve cell culture models, these models cannot accurately mimic human brains. Three-dimensional (3D) brain organoids based on human-induced pluripotent stem cells have been developed to study the human brains, but this model has rarely been used to evaluate NP neurotoxicity. We used 3D brain organoids that express cortical layer proteins to investigate the mechanisms of ZnO NP-induced neurotoxicity. Cytotoxicity caused by high levels of ZnO NPs (64 µg/mL) correlated with high intracellular Zn ion levels but not superoxide levels. Exposure to a non-cytotoxic concentration of ZnO NPs (16 µg/mL) increased the autophagy-marker proteins LC3B-II/I but decreased p62 accumulation, whereas a cytotoxic concentration of ZnO NPs (64 µg/mL) decreased LC3B-II/I proteins but did not affect p62 accumulation. Fluorescence micro-optical sectioning tomography revealed that 64 µg/mL ZnO NPs led to decreases in LC3B proteins that were more obvious at the outer layers of the organoids, which were directly exposed to the ZnO NPs. In addition to reducing LC3B proteins in the outer layers, ZnO NPs increased the number of micronuclei in the outer layers but not the inner layers (where LC3B proteins were still expressed). Adding the autophagy flux inhibitor bafilomycin A1 to ZnO NPs increased cytotoxicity and intracellular Zn ion levels, but adding the autophagy inducer rapamycin only slightly decreased cellular Zn ion levels. We conclude that high concentrations of ZnO NPs are cytotoxic to 3D brain organoids via defective autophagy and intracellular accumulation of Zn ions.

Influences of repeated exposure to low levels of TiO2 nanoparticles on Kruppel-like factors in 3D Caco-2 spheroids and mouse intestines.

Kruppel-like factors (KLFs) are a set of transcription factors (TFs) involved in the regulation of many basic biological processes, and recent studies suggested that nanoparticles (NPs) were capable to change KLFs in different models even at non-cytotoxic concentrations. In this study, we repeatedly exposed 3D Caco-2 spheroids and mice to TiO2 NPs, one of the most frequently used metal oxide NPs, and investigated the changes of KLF-signaling pathways based on RNA-sequencing. Although the internalization of TiO2 NPs did not induce cytotoxicity in vitro, repeated exposure (three times within 7 days) to 15.7 ng/ml TiO2 NPs increased KLF4 but decreased KLF6. Consistently, KLF4/KLF6-regulated gene ontology terms were altered, including those involved in the regulation of gene expression. We further verified that repeated exposure to 15.7 ng/ml TiO2 NPs increased the expression of KLF4 and proto-oncogene, bHLH transcription factor (MYC), but decreased the expression of KLF6 and activating transcription factor 3 (ATF3). But with the increase of NP concentrations, the expression of these genes was decreased. In mice following intragastrical exposure to 4.39 and 43.9 mg/kg TiO2 NPs (once a day for 5 continuous days), we observed increased expression of klf4, klf6, myc, and atf3, along with morphological changes of intestines. We concluded that repeated exposure to low levels of TiO2 NPs altered KLF-signaling pathways in intestinal cells both in vitro and in vivo.

Gas Sensing Properties of SnO2-Pd Nanoparticles Thick Film by Applying In Situ Synthesis-Loading Method.

In this study, SnO2-Pd nanoparticles(NPs) were made with an in situ synthesis-loading method. The in situ method is to simultaneously load a catalytic element during the procedure to synthesize SnO2 NPs. SnO2-Pd NPs were synthesized by using the in situ method and were heat-treated at 300 °C. As a result, tetragonal structured SnO2-Pd NPs, having an ultrafine size of less than 10 nm and a uniformly distributed Pd catalyst in the SnO2 lattice, were well made and a gas sensitive thick film with a thickness of c.a. 40 µm was well fabricated by using the NPs. Gas sensing characterization for CH4 gas indicated that the gas sensitivity, R3500/R1000, of the thick film consistent with SnO2-Pd NPs synthesized with the in situ synthesis-loading method, followed by heat-treatment at 500 °C, was enhanced to 0.59. Therefore, the in situ synthesis-loading method is available for synthesis of SnO2-Pd NPs for gas sensitive thick film.

Investigating the Effect of Surface Hydrophilicity on the Destiny of PLGA-Poloxamer Nanoparticles in an In Vivo Animal Model.

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

Paclitaxel Delivery to the Brain for Glioblastoma Treatment.

The development of paclitaxel-loaded polymeric nanoparticles for the treatment of brain tumors was investigated. Poly(lactide-glycolide) (PLGA) nanoparticles containing 10% w/w paclitaxel with a particle size of 216 nm were administered through intranasal and intravenous routes to male Sprague-Dawley rats at a dose of 5 mg/kg. Both routes of administration showed appreciable accumulation of paclitaxel in brain tissue, liver, and kidney without any sign of toxicity. The anti-proliferative effect of the nanoparticles on glioblastoma tumor cells was comparable to that of free paclitaxel.

M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma.

BACKGROUND: Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. RESULTS: Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (ß-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. CONCLUSIONS: CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC.

Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

Enhanced silver nanoparticle-induced pulmonary inflammation in a metabolic syndrome mouse model and resolvin D1 treatment.

BACKGROUND: Metabolic syndrome (MetS) exacerbates susceptibility to inhalation exposures such as particulate air pollution, however, the mechanisms responsible remain unelucidated. Previously, we determined a MetS mouse model exhibited exacerbated pulmonary inflammation 24 h following AgNP exposure compared to a healthy mouse model. This enhanced response corresponded with reduction of distinct resolution mediators. We hypothesized silver nanoparticle (AgNP) exposure in MetS results in sustained pulmonary inflammation. Further, we hypothesized treatment with resolvin D1 (RvD1) will reduce exacerbations in AgNP-induced inflammation due to MetS. RESULTS: To evaluate these hypotheses, healthy and MetS mouse models were exposed to vehicle (control) or AgNPs and a day later, treated with resolvin D1 (RvD1) or vehicle (control) via oropharyngeal aspiration. Pulmonary lung toxicity was evaluated at 3-, 7-, 14-, and 21-days following AgNP exposure. MetS mice exposed to AgNPs and receiving vehicle treatment, demonstrated exacerbated pulmonary inflammatory responses compared to healthy mice. In the AgNP exposed mice receiving RvD1, pulmonary inflammatory response in MetS was reduced to levels comparable to healthy mice exposed to AgNPs. This included decreases in neutrophil influx and inflammatory cytokines, as well as elevated anti-inflammatory cytokines. CONCLUSIONS: Inefficient resolution may contribute to enhancements in MetS susceptibility to AgNP exposure causing an increased pulmonary inflammatory response. Treatments utilizing specific resolution mediators may be beneficial to individuals suffering MetS following inhalation exposures.

Ethoxy acetalated dextran-based nanocarriers accomplish efficient inhibition of leukotriene formation by a novel FLAP antagonist in human leukocytes and blood.

Leukotrienes are pro-inflammatory lipid mediators generated by 5-lipoxygenase aided by the 5-lipoxygenase-activating protein (FLAP). BRP-201, a novel benzimidazole-based FLAP antagonist, inhibits leukotriene biosynthesis in isolated leukocytes. However, like other FLAP antagonists, BRP-201 fails to effectively suppress leukotriene formation in blood, which limits its therapeutic value. Here, we describe the encapsulation of BRP-201 into poly(lactide-co-glycolide) (PLGA) and ethoxy acetalated dextran (Ace-DEX) nanoparticles (NPs), aiming to overcome these detrimental pharmacokinetic limitations and to enhance the bioactivity of BRP-201. NPs loaded with BRP-201 were produced via nanoprecipitation and the physicochemical properties of the NPs were analyzed in-depth using dynamic light scattering (size, dispersity, degradation), electrophoretic light scattering (effective charge), NP tracking analysis (size, dispersity), scanning electron microscopy (size and morphology), UV-VIS spectroscopy (drug loading), an analytical ultracentrifuge (drug release, degradation kinetics), and Raman spectroscopy (chemical attributes). Biological assays were performed to study cytotoxicity, cellular uptake, and efficiency of BRP-201-loaded NPs versus free BRP-201 to suppress leukotriene formation in primary human leukocytes and whole blood. Both PLGA- and Ace-DEX-based NPs were significantly more efficient to inhibit leukotriene formation in neutrophils versus free drug. Whole blood experiments revealed that encapsulation of BRP-201 into Ace-DEX NPs strongly increases its potency, especially upon pro-longed (≥ 5 h) incubations and upon lipopolysaccharide-challenge of blood. Finally, intravenous injection of BRP-201-loaded NPs significantly suppressed leukotriene levels in blood of mice in vivo. These results reveal the feasibility of our pharmacological approach using a novel FLAP antagonist encapsulated into Ace-DEX-based NPs with improved efficiency in blood to suppress leukotriene biosynthesis.

Determination of ß-glucosidase activity using single-particle enumeration with Au@CeO2 nanoparticles.

A visible and sensitive assay for the quantitative detection of ß-glucosidase (ß-glu) activity based on Au@CeO2 core-shell nanoparticles (Au@CeO2 NPs) is described. As a hydrolytic enzyme, ß-glu can promote the hydrolysis of ß-arbutin to hydroquinone (HQ), which can trigger the decomposition of the CeO2 shell. With the single-particle enumeration (SPE) strategy coupled with dark field optical microscopy (DFM), an obvious color alteration of single Au@CeO2 NPs during the etching process can be observed in real-time. By statistically calculating the number of the etched nanoparticles, the ß-glu activity level can be quantified accurately. This assay displays a broad linear range from 0.5 to 50 mU⋅mL-1 and low detection limit of 0.12 mU⋅mL-1. In addition, this method was successfully used to determine ß-glu in real samples and acquires satisfactory recoveries in the range of 97.1-102.0%. This study provides a visualization analysis method for ß-glu, which may be helpful for monitoring other targets in the future.

pH-responsive glucosamine anchored polydopamine coated mesoporous silica nanoparticles for delivery of Anderson-type polyoxomolybdate in breast cancer.

AIM: This study aimed to develop novel pH-sensitive Glucosamine (Glu) targeted Polydopamine (PDA) coated mesoporous silica (SBA-15) nanoparticles (NPs) for selective delivery of anticancer Anderson-type manganese polyoxomolybdate (POMo) to breast cancer. METHODS: The POMo@SBA-PDA-Glu NPs were prepared via direct hydrothermal synthesis of SBA, POMo loading, in situ PDA post functionalization, and Glu anchoring; the chemical structures were fully studied by different characterisation methods. The anticancer activity was studied by MTT method and Annexin V-FITC apoptosis detection kit. RESULTS: The optimised NPs had a hydrodynamic size (HS) of 195 nm, a zeta potential (ZP) of -18.9 mV, a loading content percent (LC%) of 45%, and a pH-responsive release profile. The targeted NPs showed increased anticancer activity against breast cancer cell lines compared to the free POMo with the highest cellular uptake and apoptosis level in the MDA-MB-231 cells. CONCLUSIONS: POMo@SBA-PDA-Glu NPs could be a promising anticancer candidate for further studies.

MicroRNAs in T Cell-Immunotherapy.

MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge of miRNAs as T-cell targeting immunotherapeutic tools, and we offer an overview of the recent advances in miRNA delivery strategies, clinical trials and future perspectives in RNA interference technologies.