A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy.

PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.

Dual Drug Loaded Potassium-contained Graphene Oxide as a Nanocarrier in Cocktailed Drug Delivery for the Treatment of Human Breast Cancer.

BACKGROUND: The combinatorial use of anticancer drugs, dual or multiple, with a specific nanocarrier is one of the most promising attempts in drug delivery. The current work reports potassium contained graphene oxide (K-GO) as a nanocarrier in the drug delivery system of two anticancer drugs, gefitinib (GEF) and camptothecin (CPT), simultaneously. METHODS: To characterize K-GO, K-GO-related single and combined drug systems, different techniques have been performed and studied using the following spectroscopic tools, such as Thermo Gravimetric Analysis (TGA 4000), UV-visible spectroscopy, Raman spectroscopy, and Transmission electron microscopy (TEM). The in vitro cytotoxicity tests of K-GO, single drug system, and the combined drug system were also performed in the human breast cancer MDA-MB-231 cells. RESULTS: The release profile of the dual drug conjugates grafted onto the surface of K-GO was found to be up to 38% in PBS solution over 72 hours. The percentage of MDA-MB-231 cell viability was about 18% when treated with K-GO-GEF-CPT combined system; for K-GO, K-GO-GEF, and K-GO-CPT, the cell viability was 79%, 31%, and 32%, respectively. CONCLUSION: We studied the loading, release, and delivery of two anticancer drugs onto the fluorescent nanocarrier. Features, such as superb aqueous solubility, excellent biocompatibility, richness in potassium, and fluorescent nature, which can monitor the delivery of drugs, make them a promising nanocarrier for single or multiple drug delivery. Furthermore, our novel findings revealed that the loading capacity and cytotoxicity of the combined drug-loaded system are superior to the capacity of the individual drug system for human breast cancer cells.

Recent Advancements in Green Synthesis of Nanoparticles for Improvement of Bioactivities: A Review.

Natural products have widely been used in applications ranging from antibacterial, antiviral, antifungal, and various other medicinal applications. The use of these natural products was recognized way before the establishment of basic chemistry behind the disease and the chemistry of plant metabo-lites. After the establishment of plant chemistry, various new horizons evolved, and the application of natural products breached the orthodox limitations. In one such interdisciplinary area, the use of plant materials in the synthesis of nanoparticles (NPs) has exponentially emerged. This advancement has offered various environment-friendly methods where hazardous chemicals are completely replaced by natural products in the sophisticated and hectic synthesis processes. This review is an attempt to under-stand the mechanism of metal nanoparticles synthesis using plant materials. It includes details on the role of the plant's secondary metabolites in the synthesis of nanoparticles including the mechanism of action. In addition, the use of these nanomaterials has widely been discussed along with the possible mechanism behind their antimicrobial and catalytic action.

Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.

Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.

Functionalized graphene oxide as a vehicle for targeted drug delivery and bioimaging applications.

Graphene oxide (GO) has attracted tremendous attention as a most promising nanomaterial among the carbon family since it emerged as a polynomial functional tool with rational applications in diverse fields such as biomedical engineering, electrocatalysis, biosensing, energy conversion, and storage devices. Despite having certain limitations due to its irreversible aggregation performance owing largely to the strong van der Waals interactions, efforts have been made to smartly engineer its surface chemistry for realistic multimodal applications. The use of such GO-based engineered devices has increased rapidly in the last few years, principally due to its excellent properties, such as huge surface area, honeycomb-like structure allowing vacant interstitial space to accommodate compounds, sp2 hybridized carbon, improved biocompatibility and cell surface penetration due to electronic interactions. Amongst multifaceted GO dynamics, in this review, attempts are made to discuss the advanced applications of GO or graphene-based materials (GBNs) in the biomedical field involving drug or therapeutic gene delivery, dual drug or drug-gene combination targeting, special delivery of drug cocktails to the brain, stimuli-responsive release of molecular payloads, and Janus-structured smart applications for polar-nonpolar combination drug loading followed by targeting together with smart bioimaging approaches. In addition, the advantages of duel-drug delivery systems are discussed in detail. We also discuss various electronic mechanisms, and detailed surface engineering to meet microcosmic criteria for its utilization, various novel implementations of engineered GO as mentioned above, together with discussions of its inevitable toxicity or disadvantages. We hope that the target audience, belonging to biomedical engineering, pharmaceutical or material science fields, may acquire relevant information from this review which may help them design future studies in this field.

Functionalized graphene oxide as a nanocarrier for dual drug delivery applications: The synergistic effect of quercetin and gefitinib against ovarian cancer cells.

Graphene Oxide (GO) has been extensively studied in the field of biomedical sciences as one of the most promising biomaterials due to its exceptional physiochemical properties. Experts have long favored anticancer drug cocktails over single drugs, given that the former may provide a more balanced molecular basis for novel chemotherapeutic strategies. Here, we investigated a combinatorial anticancer drug treatment involving the well-proven anticancer drugs quercetin and gefitinib and compared it with gefitinib and quercetin loaded separately onto polyvinylpyrrolidone (PVP)-functionalized graphene oxide (GO-PVP). The loading and cancer cell cytotoxicity of the individual drug systems and their combined loading onto GO-PVP nanovehicles were investigated in PA-1 ovarian cancer cells and compared to their effects on IOSE-364 ovarian epithelial cells. In this report, the combined drug system loaded on the GO-PVP nanovehicle was found to be significantly more toxic than the individual drug loaded systems, as well as the free drugs, toward PA-1 cells compared to the toxicity toward IOSE-364 cells. The combined drug system loaded on the GO-PVP nanovehicle is likely to be more successful than individual drug therapy, given the stronger impact of the combinatorial approach and the efficiency of chemotherapeutic delivery.

Functionalized graphene oxides for drug loading, release and delivery of poorly water soluble anticancer drug: A comparative study.

In this work, the modification of graphene oxides (GOs) have been done with hydrophilic and biodegradable polymer, polyvinylpyrrolidone (PVP) and other excipient ß -cyclodextrin (ß-CD) through covalent functionalization for efficient loading and compatible release of sparingly water soluble aromatic anticancer drug SN-38 (7-ethyl-10-hydroxy camptothecin). The drug was loaded onto both GO-PVP and GO-ß-CD through the π-π interactions.The release of drug from both the nanocarriers were analyzed in different pH medium of pH 7 (water, neutral medium), pH 5 (acidic buffer) and pH 12 (basic buffer). The loading capacity and the cell killing activity of SN-38 loaded on functionalized GO were investigated comprehensively in human breast cancer cells MCF-7.Our findings shown that the cytotoxicity of SN-38 loaded to the polymer modified GO was comparatively higher than free SN-38. In particular, SN-38 loaded GO-PVP nanocarrier has more cytotoxic effect than GO-ß-CD nanocarrier against MCF-7 cells, indicating that SN-38 loaded GO-PVP nanocarrier can be used as promising material for drug delivery and biological applications.