Advances with Lipid-Based Nanosystems for siRNA Delivery to Breast Cancers.

Breast cancer is the most frequently diagnosed cancer among women. Breast cancer is also the key reason for worldwide cancer-related deaths among women. The application of small interfering RNA (siRNA)-based drugs to combat breast cancer requires effective gene silencing in tumor cells. To overcome the challenges of drug delivery to tumors, various nanosystems for siRNA delivery, including lipid-based nanoparticles that protect siRNA from degradation for delivery to cancer cells have been developed. These nanosystems have shown great potential for efficient and targeted siRNA delivery to breast cancer cells. Lipid-based nanosystems remain promising as siRNA drug delivery carriers for effective and safe cancer therapy including breast cancer. Lipid nanoparticles (LNPs) encapsulating siRNA enable efficient and specific silencing of oncogenes in breast tumors. This review discusses a variety of lipid-based nanosystems including cationic lipids, sterols, phospholipids, PEG-lipid conjugates, ionizable liposomes, exosomes for effective siRNA drug delivery to breast tumors, and the clinical translation of lipid-based siRNA nanosystems for solid tumors.

Recent Advances with Precision Medicine Treatment for Breast Cancer including Triple-Negative Sub-Type.

Breast cancer is a heterogeneous disease with different molecular subtypes. Breast cancer is the second leading cause of mortality in woman due to rapid metastasis and disease recurrence. Precision medicine remains an essential source to lower the off-target toxicities of chemotherapeutic agents and maximize the patient benefits. This is a crucial approach for a more effective treatment and prevention of disease. Precision-medicine methods are based on the selection of suitable biomarkers to envision the effectiveness of targeted therapy in a specific group of patients. Several druggable mutations have been identified in breast cancer patients. Current improvements in omics technologies have focused on more precise strategies for precision therapy. The development of next-generation sequencing technologies has raised hopes for precision-medicine treatment strategies in breast cancer (BC) and triple-negative breast cancer (TNBC). Targeted therapies utilizing immune checkpoint inhibitors (ICIs), epidermal growth factor receptor inhibitor (EGFRi), poly(ADP-ribose) polymerase inhibitor (PARPi), antibody-drug conjugates (ADCs), oncolytic viruses (OVs), glucose transporter-1 inhibitor (GLUT1i), and targeting signaling pathways are potential treatment approaches for BC and TNBC. This review emphasizes the recent progress made with the precision-medicine therapy of metastatic breast cancer and TNBC.

Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM).

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood-brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients.

Advances in Targeted Therapy of Breast Cancer with Antibody-Drug Conjugate.

Antibody-drug conjugates (ADCs) are a potential and promising therapy for a wide variety of cancers, including breast cancer. ADC-based drugs represent a rapidly growing field of breast cancer therapy. Various ADC drug therapies have progressed over the past decade and have generated diverse opportunities for designing of state-of-the-art ADCs. Clinical progress with ADCs for the targeted therapy of breast cancer have shown promise. Off-target toxicities and drug resistance to ADC-based therapy have hampered effective therapy development due to the intracellular mechanism of action and limited antigen expression on breast tumors. However, innovative non-internalizing ADCs targeting the tumor microenvironment (TME) component and extracellular payload delivery mechanisms have led to reduced drug resistance and enhanced ADC effectiveness. Novel ADC drugs may deliver potent cytotoxic agents to breast tumor cells with reduced off-target effects, which may overcome difficulties related to delivery efficiency and enhance the therapeutic efficacy of cytotoxic cancer drugs for breast cancer therapy. This review discusses the development of ADC-based targeted breast cancer therapy and the clinical translation of ADC drugs for breast cancer treatment.

Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis.

The innovative development of nanomedicine has promised effective treatment options compared to the standard therapeutics for cancer therapy. However, the efficiency of EPR-targeted nanodrugs is not always pleasing as it is strongly prejudiced by the heterogeneity of the enhanced permeability and retention effect (EPR). Targeting the dynamics of the EPR effect and improvement of the therapeutic effects of nanotherapeutics by using EPR enhancers is a vital approach to developing cancer therapy. Inadequate data on the efficacy of EPR in humans hampers the clinical translation of cancer drugs. Molecular targeting, physical amendment, or physiological renovation of the tumor microenvironment (TME) are crucial approaches for improving the EPR effect. Advanced imaging technologies for the visualization of EPR-induced nanomedicine distribution in tumors, and the use of better animal models, are necessary to enhance the EPR effect. This review discusses strategies to enhance EPR effect-based drug delivery approaches for cancer therapy and imaging technologies for the diagnosis of EPR effects. The effort of studying the EPR effect is beneficial, as some of the advanced nanomedicine-based EPR-enhancing approaches are currently undergoing clinical trials, which may be helpful to improve EPR-induced drug delivery and translation to clinics.

Biopolymer-Based Nanosystems for siRNA Drug Delivery to Solid Tumors including Breast Cancer.

Nanobiopolymers such as chitosan, gelatin, hyaluronic acid, polyglutamic acid, lipids, peptides, exosomes, etc., delivery systems have prospects to help overwhelmed physiological difficulties allied with the delivery of siRNA drugs to solid tumors, including breast cancer cells. Nanobiopolymers have favorable stimuli-responsive properties and therefore can be utilized to improve siRNA delivery platforms to undruggable MDR metastatic cancer cells. These biopolymeric siRNA drugs can shield drugs from pH degradation, extracellular trafficking, and nontargeted binding sites and are consequently suitable for drug internalization in a controlled-release fashion. In this review, the utilization of numerous biopolymeric compounds such as siRNA drug delivery systems for MDR solid tumors, including breast cancers, will be discussed.

Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics.

Metal oxide nanoparticles have attracted increased attention due to their emerging applications in cancer detection and therapy. This study envisioned to highlight the great potential of metal oxide NPs due to their interesting properties including high payload, response to magnetic field, affluence of surface modification to overcome biological barriers, and biocompatibility. Mammogram, ultrasound, X-ray computed tomography (CT), MRI, positron emission tomography (PET), optical or fluorescence imaging are used for breast imaging. Drug-loaded metal oxide nanoparticle delivered to the breast cancer cells leads to higher drug uptake. Thus, enhanced the cytotoxicity to target cells compared to free drug. The drug loaded metal oxide nanoparticle formulations hold great promise to enhance efficacy of breast cancer therapy including multidrug resistant (MDR) and metastatic breast cancers. Various metal oxides including magnetic metal oxides and magnetosomes are of current interests to explore cancer drug delivery and diagnostic efficacy especially for metastatic breast cancer. Metal oxide-based nanocarrier formulations are promising for their usage in drug delivery and release to breast cancer cells, cancer diagnosis and their clinical translations.

Recent Development in Metallic Nanoparticles for Breast Cancer Therapy and Diagnosis.

Metal-based nanoparticles are very promising for their applications in cancer diagnosis, drug delivery and therapy. Breast cancer is the major reason of death in woman especially in developed countries including EU and USA. Due to the heterogeneity of cancer cells, nanoparticles are effective as therapeutics and diagnostics. Anti-cancer therapy of breast tumors is challenging because of highly metastatic progression of the disease to brain, bone, lung, and liver. Magnetic nanoparticles are crucial for metastatic breast cancer detection and protection. This review comprehensively discusses the application of nanomaterials as breast cancer therapy, therapeutics, and diagnostics.

Recent Advances in Synthesis and Applications of Single-Atom Catalysts for Rechargeable Batteries.

The rapid development of flexible and wearable optoelectronic devices, demanding the superior, reliable, and ultra-long cycling energy storage systems. But poor performances of electrode materials used in energy devices are main obstacles. Recently, single-atom catalysts (SACs) are considered as emerging and potential candidates as electrode materials for battery devices. Herein, we have discussed the recent methods for the fabrication of SACs for rechargeable metal-air batteries, metal-CO2 batteries, metal-sulfur batteries, and other batteries, following the recent advances in assembling and performance of these batteries by using SACs as electrode materials. The role of SACs to solve the bottle-neck problems of these energy storage devices and future perspectives are also discussed.

Neutrophils as an emerging therapeutic target and tool for cancer therapy.

Activation of neutrophils is necessary for the protection of the host against microbial infection. This property can be used as mode of therapy for cancer treatment. Neutrophils have conflicting dual functions in cancer as either a tumor promoter or inhibitor. Neutrophil-based drug delivery has achieved increased attention in pre-clinical models. This review addresses in detail the different neutrophil constituents, the conflicting function of neutrophils and activation of the neutrophil as an important target of therapy for cancer treatment, and use of neutrophils or neutrophil membrane-derived vesicles as vehicles for drug delivery and targeting.

Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment.

Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy.

Advances in siRNA delivery strategies for the treatment of MDR cancer.

RNA interference (RNAi) represents a promising therapeutic method that uses siRNA for cancer treatment. Although the RNAi technique has been increasingly used for clinical trials, systemic siRNA delivery into targeted cells is still challenging. The barriers impeding siRNA therapeutics delivery and impacting the treatment outcome must overcome with negligible systemic toxicity for a desirable and successful delivery of siRNA to MDR cancer cells. Nano delivery strategies have been investigated for nanocarrier functionalization, cancer immunotherapy and cancer targeting. Lipid nanoparticles (LNPs), dynamic polyconjugates (DPC™), GalNAc-siRNA conjugates, exosome and RBC systems have shown potential for efficient delivery of siRNA to cancer cells. Delivery of siRNA to tumor cells, immune cells to regulate T cell functions for immunotherapy are promising approaches.

Photocatalytic performance, anti-bacterial activities and 3-chlorophenol sensor fabrication using MnAl2O4·ZnAl2O4 nanomaterials.

A MnAl2O4·ZnAl2O4 nanomaterial was synthesized by co-precipitation and characterized by XRD, SEM, EDS, TEM, AFM, FTIR, PL, CV and EIS. The photocatalytic activity of the nanocomposite against MV dye and its MDR anti-bacterial functions were studied. The nanocomposite shows excellent photocatalytic as well as anti-bacterial activity. A MnAl2O4·ZnAl2O4 nanomaterial/Nafion/GCE electrode was fabricated and implemented as the working electrode of a 3-CP sensor. The sensor exhibited good sensitivity, with the lowest detection limit, fast response time, large linear dynamic range (LDR), and long-term stability in the chemical environment. The estimated sensitivity is 70.07 µA mM-1 cm-2. The LDR, limit of detection (LOD), and limit of quantification (LOQ) are 0.1 nM to 0.01 M, 0.0014 ± 0.0001 nM, and 0.004 nM, respectively. The MnAl2O4·ZnAl2O4 nanomaterial/Nafion/GCE is a promising fabricated sensor probe for the selective detection of 3-CP for the environmental safety and healthcare fields on a large scale.

Enhancing the Performance of Dye Sensitized Solar Cells Using Silver Nanoparticles Modified Photoanode.

In this study, silver nanoparticles were synthesized, characterized, and applied to a dye-sensitized solar cell (DSSC) to enhance the efficiency of solar cells. The synthesized silver nanoparticles were characterized with UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, and field emission scanning electron microscopy. The silver nanoparticles infused titanium dioxide film was also characterized by Fourier transform infrared and Raman spectroscopy. The performance of DSSC fabricated with silver nanoparticle-modified photoanode was compared with that of a control group. The current and voltage characteristics of the devices as well as the electrochemical impedance measurements were also carried out to assess the performance of the fabricated solar cells. The solar-to-electric efficiency of silver nanoparticles based DSSC was 1.76%, which is quite remarkable compared to the 0.98% realized for DSSC fabricated without silver nanoparticles.

siRNA based drug design, quality, delivery and clinical translation.

Gene silencing by RNA interference represents a promising therapeutic approach. The development of carriers, e.g., polymers, lipids, peptides, antibodies, aptamers, small molecules, exosome and red blood cells, is crucial for the systemic delivery of siRNA. Cell-specific targeting ligands in the nano-carriers can improve the pharmacokinetics, biodistribution, and selectivity of siRNA therapeutics. The safety, effectiveness, quality and prosperity of production and manufacturing are important considerations for selecting the appropriate siRNA carriers. Efficacy of systemic delivery of siRNA requires considerations of trafficking through the blood, off-target effects, innate immune response and endosomal escape avoiding lysosomal degradation for entering into RNAi process. Multifunctional nanocarriers with stimuli-responsive properties such as pH, magnetic and photo-sensitive segments can enhance the efficacy of siRNA delivery. The improved preclinical characterization of suitable siRNA drugs, good laboratory practice, that reduce the differences between in vitro and in vivo results may increase the success of siRNA drugs in clinical settings.

Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA.

Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells. Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1. This formulation was further modified with monoclonal antibodies 2C5 with nucleosome-restricted specificity that effectively recognized cancer cells via the cell-surface-bound nucleosomes. Micelles with attached 2C5 antibodies significantly enhanced cellular association and tumor killing in both monolayer and spheroid tumor models as well as in vivo in experimental animals compared to the nontargeted formulations.

Enhanced visible light-mediated photocatalysis, antibacterial functions and fabrication of a 3-chlorophenol sensor based on ternary Ag2O·SrO·CaO.

A novel multi-metal oxide nanocomposite, Ag2O·SrO·CaO, was synthesized by a facile co-precipitation method followed by calcinations. The synthesized nanocomposite was characterized by XRD, FESEM, EDS, TEM, FTIR spectroscopy and photoluminescence (PL) spectroscopy. The composite showed enhanced photocatalytic activity under visible light irradiation and excellent anti-bacterial performance against both Gram-positive and Gram-negative bacteria. Here, the synthesized Ag2O·SrO·CaO nanomaterials were deposited on a glassy carbon electrode (GCE) in the form of a thin film to fabricate the desired electrochemical sensor and subjected to I-V analysis of 3-chlorophenol (3-CP) in a phosphate buffer solution (PBS). A calibration curve was plotted from the linear relation of current versus concentration and used to calculate the sensitivity (8.9684 µA µM-1 cm-2), linear dynamic range (LDR, 0.1 nM to 0.01 mM) and lower limit of detection (DL, 97.12 ± 4.86 pM). The analytical parameters of the sensor such as response time, reproducibility and long-term stability in the detection of 3-CP were reliable. Finally, it was used to analyze real samples collected from various environmental sources and found to be acceptable.

Photocatalysis, photoinduced enhanced anti-bacterial functions and development of a selective m-tolyl hydrazine sensor based on mixed Ag·NiMn2O4 nanomaterials.

In this work, a tri-metal based nanocomposite was synthesized and characterized. A detailed investigation of the photocatalytic dye degradation efficiency of the nanocomposite under visible light showed promising results in a wide pH range, both acidic and basic medium. Studies on anti-bacterial activity against seven pathogenic bacteria, including both Gram positive and Gram negative species, were conducted in the presence and absence of light and compared with the standard antibiotic gentamicin. The minimum inhibitory concentration (MIC) values of Ag·NiMn2O4 against multidrug-resistant (MDR) pathogens ranged from 0.008 to 0.65 µg µL-1, while the minimum bactericidal concentration (MBC) was found to be 0.0016 µg µL-1. The nanomaterial, Ag·NiMn2O4 was deposited onto the surface of a glassy carbon electrode (GCE; 0.0316 cm2) as a thin film to fabricate the chemical sensor probe. The proposed sensor showed linear current (vs. concentration) response to m-THyd (m-tolyl hydrazine) from 1.0 pM to 0.01 mM, which is denoted as the linear dynamic range (LDR). The estimated sensitivity and detection limit of the m-THyd sensor were found to be 47.275 µA µM-1 cm-2 and 0.97 ± 0.05 pM, respectively. As a potential sensor, it is reliable due to its good reproducibility, rapid response, higher sensitivity, working stability for long duration and efficiency in the analysis of real environmental samples.

Efficient nanocarriers of siRNA therapeutics for cancer treatment.

Nanocarriers as drug delivery systems are promising and becoming popular, especially for cancer treatment. In addition to improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing them in a hydrophobic core, nanocarriers allow cancer-specific combination drug deliveries by inherent passive targeting phenomena and adoption of active targeting strategies. Nanoparticle-drug formulations can enhance the safety, pharmacokinetic profiles, and bioavailability of locally or systemically administered drugs, leading to improved therapeutic efficacy. Gene silencing by RNA interference (RNAi) is rapidly developing as a personalized field of cancer treatment. Small interfering RNAs (siRNAs) can be used to switch off specific cancer genes, in effect, "silence the gene, silence the cancer." siRNA can be used to silence specific genes that produce harmful or abnormal proteins. The activity of siRNA can be used to harness cellular machinery to destroy a corresponding sequence of mRNA that encodes a disease-causing protein. At present, the main barrier to implementing siRNA therapies in clinical practice is the lack of an effective delivery system that protects the siRNA from nuclease degradation, delivers to it to cancer cells, and releases it into the cytoplasm of targeted cancer cells, without creating adverse effects. This review provides an overview of various nanocarrier formulations in both research and clinical applications with a focus on combinations of siRNA and chemotherapeutic drug delivery systems for the treatment of multidrug resistant cancer. The use of various nanoparticles for siRNA-drug delivery, including liposomes, polymeric nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and red blood cells for targeted drug delivery in cancer is discussed.

Enhanced photocatalytic activity and ultra-sensitive benzaldehyde sensing performance of a SnO2·ZnO·TiO2 nanomaterial.

The synthesis of a ternary SnO2·ZnO·TiO2 nanomaterial (NM) by a simple co-precipitation method and its potential applications as an efficient photocatalyst and chemical sensor have been reported. The synthesized nanomaterial was fully characterized by XRD, SEM, EDS, XPS, FTIR, AFM and photoluminescence studies. This nanomaterial exhibited enhanced efficiency in photo-catalysis of Methyl Violet 6b (MV) dye degradation. The observed photocatalyst efficiency of the SnO2·ZnO·TiO2 nanomaterial was 100% under UV light at pH 9. Moreover, it lost around 12% efficiency over five reuses. The PL properties with changing excitation energy were also reported. Glassy carbon electrode (GCE) was modified with the SnO2·ZnO·TiO2 nanomaterial by an efficient electrochemical technique to develop a chemical sensor for selective benzaldehyde. Hazardous benzaldehyde was carefully chosen as a target analyte by a selectivity study; it displays a rapid response towards the SnO2·ZnO·TiO2/Nafion/GCE sensor probe in electrochemical sensing. It also shows superb sensitivity, an ultra-low detection limit, long-term stability, and very good repeatability and reproducibility. In this study, a linear calibration plot was obtained for 0.1 nM to 1.0 mM aqueous benzaldehyde solutions, with a sensitivity value of 4.35 nA µM-1 cm-2 and an exceptionally low detection limit (LOD) of 3.2 ± 0.1 pM (S/N = 3). Hence, a chemical sensor modified with SnO2·ZnO·TiO2/GCE may be a promising sensor in the determination of toxic chemicals in the environmental and healthcare fields.