Lipid-Based Nanocarriers for Targeted Gene Delivery in Lung Cancer Therapy: Exploring a Novel Therapeutic Paradigm.

Lung cancer is a significant cause of cancer-related death worldwide. It can be broadly categorised into small-cell lung cancer (SCLC) and Non-small cell lung cancer (NSCLC). Surgical intervention, radiation therapy, and the administration of chemotherapeutic medications are among the current treatment modalities. However, the application of chemotherapy may be limited in more advanced stages of metastasis due to the potential for adverse effects and a lack of cell selectivity. Although small-molecule anticancer treatments have demonstrated effectiveness, they still face several challenges. The challenges at hand in this context comprise insufficient solubility in water, limited bioavailability at specific sites, adverse effects, and the requirement for epidermal growth factor receptor inhibitors that are genetically tailored. Bio-macromolecular drugs, including small interfering RNA (siRNA) and messenger RNA (mRNA), are susceptible to degradation when exposed to the bodily fluids of humans, which can reduce stability and concentration. In this context, nanoscale delivery technologies are utilised. These agents offer encouraging prospects for the preservation and regulation of pharmaceutical substances, in addition to improving the solubility and stability of medications. Nanocarrier-based systems possess the notable advantage of facilitating accurate and sustained drug release, as opposed to traditional systemic methodologies. The primary focus of scientific investigation has been to augment the therapeutic efficacy of nanoparticles composed of lipids. Numerous nanoscale drug delivery techniques have been implemented to treat various respiratory ailments, such as lung cancer. These technologies have exhibited the potential to mitigate the limitations associated with conventional therapy. As an illustration, applying nanocarriers may enhance the solubility of small-molecule anticancer drugs and prevent the degradation of bio-macromolecular drugs. Furthermore, these devices can administer medications in a controlled and extended fashion, thereby augmenting the therapeutic intervention's effectiveness and reducing adverse reactions. However, despite these promising results, challenges remain that must be addressed. Multiple factors necessitate consideration when contemplating the application of nanoparticles in medical interventions. To begin with, the advancement of more efficient delivery methods is imperative. In addition, a comprehensive investigation into the potential toxicity of nanoparticles is required. Finally, additional research is needed to comprehend these treatments' enduring ramifications. Despite these challenges, the field of nanomedicine demonstrates considerable promise in enhancing the therapy of lung cancer and other respiratory diseases.

Smart Nanobiomaterials for Gene Delivery in Localized Cancer Therapy: An Overview from Emerging Materials and Devices to Clinical Applications.

Researchers in various fields continue to discover improved ways of local delivery of drugs to specific locations and try to increase the efficiency of these methods. Extensive research has been done on smart nano-biomaterials for drug delivery systems (DDS) in different dimensions. With the advancement of biomedical nanotechnology, conventional smart DDS with stimuli- responsive capability has been developed. Smart nano-biomaterials can respond to environmental changes caused by endogenous or exogenous elements: endogenous factors such as environmental pH, temperature gradient, enzymes, oxidation, and reduction potential. As well as exogenous factors, including light radiation, ultrasound, electric and magnetic fields. Currently, smart DDSs count as a major category in DDS and disease treatment. Currently, smart DDS are of great interest in drug delivery and treatment of diseases. With the improvements in gene and protein therapy, new methods have been presented to treat diseases without effective conventional treatment, especially cancer. Finally, the use of nanoparticles expanded due to the need for appropriate gene and protein delivery systems. This review discusses the advantages of protein and gene therapy, their challenges, and gene and protein delivery systems with nanoparticle-based delivery.

Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions.

Heart muscle injury and an elevated troponin level signify myocardial infarction (MI), which may result in defective and uncoordinated segments, reduced cardiac output, and ultimately, death. Physicians apply thrombolytic therapy, coronary artery bypass graft (CABG) surgery, or percutaneous coronary intervention (PCI) to recanalize and restore blood flow to the coronary arteries, albeit they were not convincingly able to solve the heart problems. Thus, researchers aim to introduce novel substitutional therapies for regenerating and functionalizing damaged cardiac tissue based on engineering concepts. Cell-based engineering approaches, utilizing biomaterials, gene, drug, growth factor delivery systems, and tissue engineering are the most leading studies in the field of heart regeneration. Also, understanding the primary cause of MI and thus selecting the most efficient treatment method can be enhanced by preparing microdevices so-called heart-on-a-chip. In this regard, microfluidic approaches can be used as diagnostic platforms or drug screening in cardiac disease treatment. Additionally, bioprinting technique with whole organ 3D printing of human heart with major vessels, cardiomyocytes and endothelial cells can be an ideal goal for cardiac tissue engineering and remarkable achievement in near future. Consequently, this review discusses the different aspects, advancements, and challenges of the mentioned methods with presenting the advantages and disadvantages, chronological indications, and application prospects of various novel therapeutic approaches.

Synthesis, optimization, and cell response investigations of natural-based, thermoresponsive, injectable hydrogel: An attitude for 3D hepatocyte encapsulation and cell therapy.

For the purpose of developing a 3D vehicle for the delivery of hepatocytes in cell therapy, the improved system of crosslinker and new gelling agent combinations consisting of glycerophosphate and sodium hydrogen carbonate have been employed to produce injectable, thermoresponsive hydrogels based on chitosan and silk fibroin. Adjusting the polymer-to-gelling agent ratio and utilizing a chemical crosslinker developed hydrogel scaffolds with optimal gelling time and pH. Applying sodium hydrogen carbonate neutralizes chitosan while keeping its thermoresponsive characteristics and decreases glycerophosphate from 60% to 30%. Genipin boosts the mechanical properties of hydrogel without affecting the gel time. Due to their stable microstructure and lower amine availability, genipin-containing materials have a low swelling ratio, around six compared to eight for those without genipin. Hydrogels that are crosslinked degrade about half as fast as those that are not. The slowerr degradation of Silk fibroin compared to chitosan makes it an efficient degradation inhibitor in silk-containing formulations. All of the optimized samples showed less than 5% hemolytic activity, indicating that they lacked hemolytic characteristics. The acceptable cell viability in crosslinked hydrogels ranges from 72% to 91% due to the decreasing total salt concentration, which protects cells from hyperosmolality. The pH of hydrogels and their interstitial pores kept most encapsulated cells alive and functioning for 24 h. Urea levels are higher in the encapsulation condition compared to HepG2 cultivated alone, and this may be due to cell-matrix interactions that boost liver-specific activity. Urea synthesis in genipin crosslinked hydrogels increased dramatically from day 1 (about 4 mg dl-1) to day 3 (approximately 6 mg dl-1), suggesting the enormous potential of these hydrogels for cell milieu preparation. All mentioned findings represent that the optimized system may be a promising candidate for liver regeneration.

Evaluation of cell viability and T2 relaxivity of fluorescein conjugated SPION-PAMAM third generation nanodendrimers for bioimaging.

This study has investigated the possibility of using fluorescent dendronized magnetic nanoparticles (FDMNPs) for potential applications in drug delivery and imaging. FDMNPs were first synthesized, characterized and then the effect of Polyamidoamine (PAMAM) dendrimer functionalization and fluorescein isothiocyanate (FITC) conjugation on biocompatibility of superparamagnetic iron oxide nanoparticles (SPIONs) was evaluated. The nanostructures' cytotoxicity tests were performed at different concentrations from 10 to 500 µg/mL using MCF-7 and L929 cell lines. IC50 in MTT assay were 139.22 and 201.88 µg/mL for DMNP incubated L929 and MCF-7 cell lines respectively, whereas the cell viability for FDMNPs did not decrease to 50%. The results showed that FITC conjugation diminishes the toxicity of dendronized magnetic nanoparticles (DMNPs) mainly due to the reduction of surface charge. DMNP appears to be cytotoxic at the concentration levels being used for both cell lines. On the contrary, FDMNPs showed more biocompatibility and cell viability of MCF-7 and L929 cell lines at all concentrations. The fluorescence microscopy of FDMNPs incubated with MCF-7 cells showed a successful localization of cells indicating their ability for applications such as a magnetic fluorescent probe in cell studies and imaging purposes. T2 relaxivity measurements demonstrated the applicability of the synthesized nanostructures as the contrast agents in tissue differential assessment by altering their relaxation times. In our case, the r2 relaxivity of FDMNPs was measured as 103.67 mM(-1)S(-1).

Comparison of health related quality of life between two groups of veteran and non-veteran spinal cord injured patients.

BACKGROUND: Patients with spinal cord injury (SCI) have a lower health related quality of life (HRQOL) compared to both healthy controls and the normal population. The aim of this study was to compare HRQOL between two groups of veteran and non-veteran SCI patients. METHODS: All male paraplegic non-veterans who had sustained complete SCI before 1988 and were residents of Tehran province (Iran), and a similar group of SCI veterans who consecutively participated in a health screening program were enrolled in this study. Patients fewer than 35 and older than 65 years of age were not included in this study. The participants were interviewed based on the Persian version of SF-36 questionnaire by two psychologists. Eight sub-scales and two physical and mental component summaries of the instrument were assessed. We used chi-square, odds ratio, Mann-Whitney U, independent t-test and linear regression for analysis. RESULTS: Overall, 25 veterans and 22 non-veterans were enrolled in the study. The mean age, time since injury and the presence of comorbid illnesses were not significantly different between the two groups (P>0.05). A greater number of veterans were married (p= 0.003) and employed (p= 0.047). On average, veterans had more years of formal education than non-veterans (p= 0.001). The mean (SD) bodily pain sub-scale was 72.73(31.253) for non-veterans and 49.7 (28.287) for veterans (p=0.011). Absence of comorbid illnesses was associated with a better physical component summary (p< 0.001). Employment was associated with a better mental component summary (p= 0.022). CONCLUSION: We did not find any differences in HRQOL between the two groups except for the bodily pain sub-scale. Further studies with larger sample sizes are recommended.