scholarly journals Green Metallic Nanoparticles for Cancer Therapy: Evaluation Models and Cancer Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1719
Author(s):  
Ernesto Tinajero-Díaz ◽  
Daniela Salado-Leza ◽  
Carmen Gonzalez ◽  
Moisés Martínez Velázquez ◽  
Zaira López ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Ag Nanoparticles ◽  
Metallic Nanoparticles ◽  
Bioactive Molecules ◽  
General Idea ◽  
Biological Assessment ◽  
In Vivo Models ◽  
Recent Advances ◽  
Evaluation Models

Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.

scholarly journals DNAzymes, Novel Therapeutic Agents in Cancer Therapy: A Review of Concepts to Applications

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
I. B. K. Thomas ◽  
K. A. P. Gaminda ◽  
C. D. Jayasinghe ◽  
D. T. Abeysinghe ◽  
R. Senthilnithy
Keyword(s):  
Nucleic Acid ◽  
Cancer Therapy ◽  
Cancer Drug ◽  
Clinical Settings ◽  
Full Potential ◽  
In Vivo Models ◽  
Recent Advances ◽  
Catalytic Dna

The past few decades have witnessed a rapid evolution in cancer drug research which is aimed at developing active biological interventions to regulate cancer-specific molecular targets. Nucleic acid-based therapeutics, including ribozymes, antisense oligonucleotides, small interference RNA (siRNA), aptamer, and DNAzymes, have emerged as promising candidates regulating cancer-specific genes at either the transcriptional or posttranscriptional level. Gene-specific catalytic DNA molecules, or DNAzymes, have shown promise as a therapeutic intervention against cancer in various in vitro and in vivo models, expediting towards clinical applications. DNAzymes are single-stranded catalytic DNA that has not been observed in nature, and they are synthesized through in vitro selection processes from a large pool of random DNA libraries. The intrinsic properties of DNAzymes like small molecular weight, higher stability, excellent programmability, diversity, and low cost have brought them to the forefront of the nucleic acid-based therapeutic arsenal available for cancers. In recent years, considerable efforts have been undertaken to assess a variety of DNAzymes against different cancers. However, their therapeutic application is constrained by the low delivery efficiency, cellular uptake, and target detection within the tumour microenvironment. Thus, there is a pursuit to identify efficient delivery methods in vivo before the full potential of DNAzymes in cancer therapy is realized. In this light, a review of the recent advances in the use of DNAzymes against cancers in preclinical and clinical settings is valuable to understand its potential as effective cancer therapy. We have thus sought to firstly provide a brief overview of construction and recent improvements in the design of DNAzymes. Secondly, this review stipulates the efficacy, safety, and tolerability of DNAzymes developed against major hallmarks of cancers tested in preclinical and clinical settings. Lastly, the recent advances in DNAzyme delivery systems along with the challenges and prospects for the clinical application of DNAzymes as cancer therapy are also discussed.

scholarly journals Two Decades of Triazine Dendrimers

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4774
Author(s):  
Eric E. Simanek
Keyword(s):  
Genetic Material ◽  
Structural Complexity ◽  
Bioactive Molecules ◽  
Bioactive Materials ◽  
In Vivo Models ◽  
Tumor Subtypes ◽  
Gas Streams

For two decades, methods for the synthesis and characterization of dendrimers based on [1,3,5]-triazine have been advanced by the group. Motivated by the desire to generate structural complexity on the periphery, initial efforts focused on convergent syntheses, which yielded pure materials to generation three. To obtain larger generations of dendrimers, divergent strategies were pursued using iterative reactions of monomers, sequential additions of triazine and diamines, and ultimately, macromonomers. Strategies for the incorporation of bioactive molecules using non-covalent and covalent strategies have been explored. These bioactive materials included small molecule drugs, peptides, and genetic material. In some cases, these constructs were examined in both in vitro and in vivo models with a focus on targeting prostate tumor subtypes with paclitaxel conjugates. In the materials realm, the use of triazine dendrimers anchored on solid surfaces including smectite clay, silica, mesoporous alumina, polystyrene, and others was explored for the separation of volatile organics from gas streams or the sequestration of atrazine from solution. The combination of these organics with metal nanoparticles has been probed. The goal of this review is to summarize these efforts.

scholarly journals Recent Advances in Understanding and Engineering Polyketide Synthesis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 208 ◽  
Author(s):  
Wenjun Zhang ◽  
Joyce Liu
Keyword(s):  
Biochemical Analysis ◽  
Polyketide Synthase ◽  
Bioactive Molecules ◽  
New Developments ◽  
Recent Advances ◽  
Fundamental Understanding ◽  
Block Formation ◽  
Enzymatic Machinery

Polyketides are a diverse group of natural products that form the basis of many important drugs. The engineering of the polyketide synthase (PKS) enzymes responsible for the formation of these compounds has long been considered to have great potential for producing new bioactive molecules. Recent advances in this field have contributed to the understanding of this powerful and complex enzymatic machinery, particularly with regard to domain activity and engineering, unique building block formation and incorporation, and programming rules and limitations. New developments in tools for in vitro biochemical analysis, full-length megasynthase structural studies, and in vivo heterologous expression will continue to improve our fundamental understanding of polyketide synthesis as well as our ability to engineer the production of polyketides.

scholarly journals The Good, the Bad, the Question–H19 in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1261 ◽  
Author(s):  
Lysann Tietze ◽  
Sonja M. Kessler
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Therapy ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Human Patient ◽  
In Vivo Models ◽  
Study Results ◽  
Novel Target

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is challenging to treat due to its typical late diagnosis, mostly at an advanced stage. Therefore, there is a particular need for research in diagnostic and prognostic biomarkers and therapeutic targets for HCC. The use of long noncoding (lnc) RNAs can widen the list of novel molecular targets improving cancer therapy. In hepatocarcinogenesis, the role of the lncRNA H19, which has been known for more than 30 years now, is still controversially discussed. H19 was described to work either as a tumor suppressor in vitro and in vivo, or to have oncogenic features. This review attempts to survey the conflicting study results and tries to elucidate the potential reasons for the contrary findings, i.e., different methods, models, or readout parameters. This review encompasses in vitro and in vivo models as well as studies on human patient samples. Although the function of H19 in HCC remains elusive, a short outlook summarizes some ideas of using the H19 locus as a novel target for liver cancer therapy.

scholarly journals Protein Hydrolysates from Anchovy (Engraulis encrasicolus) Waste: In Vitro and In Vivo Biological Activities

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 86 ◽  
Author(s):  
Alessia Giannetto ◽  
Emanuela Esposito ◽  
Marika Lanza ◽  
Sabrina Oliva ◽  
Kristian Riolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biological Activities ◽  
Protein Hydrolysates ◽  
Bioactive Molecules ◽  
Nutritional Properties ◽  
Fish Waste ◽  
In Vivo Models ◽  
Engraulis Encrasicolus

Fish waste utilization to obtain protein hydrolysates has been demonstrated to be a useful strategy to face both environmental and economic impacts while obtaining high-value products with remarkable biological and nutritional properties. In the present study, protein hydrolysates obtained from anchovy Engraulis encrasicolus (APH) by-products were assessed for their potential biological activities in both in vitro and in vivo models. The treatment with APH exerted a significant protection against LPS-induced inflammation in RAW 264.7 cells, decreasing the protein expression of pro-inflammatory mediators (i.e., COX-2) and inhibiting the nuclear translocation of NF-κB through IκB-α. Moreover, APH modulated the expression of iNOS, MnSOD and HO-1, thus decreasing the severity of oxidative stress. The supplementation of APH in the diet of ApoE knockout mice down-regulated the proinflammatory cytokines (i.e., TNF-α, IL-1α, IL-1β, IL-6) in both aorta and heart tissues, and modulated the expression of oxidative stress-related genes (Cu/ZnSod, MnSod, Cat, Gpx and Ho), indicating that APH can exert a beneficial role, having anti-inflammatory and antioxidant activities. The nutritional properties of APH, together with their biological activities herein reported, highlight the possibility of obtaining bioactive molecules from fish waste and encourage their use as potential nutraceuticals in food and pharmaceutical industries in the next future.

Synthetic Peptide Libraries: From Random Mixtures to In Vivo Testing

2020 ◽  
Vol 27 (6) ◽  
pp. 997-1016 ◽  
Author(s):  
Annamaria Sandomenico ◽  
Andrea Caporale ◽  
Nunzianna Doti ◽  
Simon Cross ◽  
Gabriele Cruciani ◽  
...  
Keyword(s):  
Synthetic Peptide ◽  
Peptide Libraries ◽  
Chemical Diversity ◽  
Bioactive Molecules ◽  
In Vivo Models ◽  
Lead Compounds ◽  
In Vivo Testing ◽  
Speed Up ◽  
New Compounds

Combinatorially generated molecular repertoires have been largely used to identify novel bioactive compounds. Ever more sophisticated technological solutions have been proposed to simplify and speed up such process, expanding the chemical diversity space and increasing the prospect to select new molecular entities with specific and potent activities against targets of therapeutic relevance. In this context, random mixtures of oligomeric peptides were originally used and since 25 years they represent a continuous source of bioactive molecules with potencies ranging from the sub-nM to microM concentration. Synthetic peptide libraries are still employed as starting “synthetic broths” of structurally and chemically diversified molecular fragments from which lead compounds can be extracted and further modified. Thousands of studies have been reported describing the application of combinatorial mixtures of synthetic peptides with different complexity and engrafted on diverse structural scaffolds for the identification of new compounds which have been further developed and also tested in in vivo models of relevant diseases. We briefly review some of the most used methodologies for library preparation and screening and the most recent case studies appeared in the literature where compounds have reached at least in vivo testing in animal or similar models. Recent technological advancements in biotechnology, engineering and computer science have suggested new options to facilitate the discovery of new bioactive peptides. In this instance, we anticipate here a new approach for the design of simple but focused tripeptide libraries against druggable cavities of therapeutic targets and its complementation with existing approaches.

scholarly journals Lipid-Based Nanocarriers Provide Prolonged Anticancer Activity for Palbociclib: In Vitro and in Vivo Evaluations

2021 ◽  
Author(s):  
Parichehr Hassanzadeh ◽  
Elham Arbabi ◽  
Fatemeh Rostami
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Survival Rates ◽  
Physicochemical Characteristics ◽  
In Vivo Models ◽  
Estrogen Receptor Positive

Breast cancer therapy has remained one of the major healthcare challenges. Based on the critical role of cyclin-dependent kinase 4/6 (CDK 4/6) in cell cycle progression, targeting this signaling appears promising for cancer therapy. Palbociclib, a selective CDKs 4/6 inhibitor, is the first-line treatment for estrogen receptor-positive breast cancer. However, poor absorption or side effects may negatively affect its efficiency. This prompted us to incorporate palbociclib into the nanostructured lipid carriers (NLCs) and evaluate the anticancer effect of the nanoformulation (Pa-NLCs) in in vitro and in vivo models of breast cancer. Pa-NLCs were developed by high-pressure homogenization followed by assessment of the physicochemical characteristics and bioactivities in MCF-7 breast cancer cells and female Wistar rats exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The prepared Pa-NLCs demonstrated suitable physicochemical characteristics, including the controlled release pattern, efficient cellular uptake, and cytotoxicity, while free palbociclib failed to show significant effects. Rats treated with Pa-NLCs exhibited significantly reduced tumor volumes, increased survival rates, and histopathological improvement. Free palbociclib was significantly less efficient than Pa-NLCs. Pa-NLCs, by improving the pharmacological profile of palbociclib and providing longer-lasting effects, can be considered as a promising nanoformulation against breast cancer.

The Potential Applications of Stem Cells for Cancer Treatment

2021 ◽  
Vol 16 ◽  
Author(s):  
Malikeh Rad Niknam ◽  
Farnoosh Attari
Keyword(s):  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Bystander Effect ◽  
Suicide Gene ◽  
Oncolytic Viruses ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
Potential Applications

: Scientists encounter many obstacles in traditional cancer therapies, including the side effects on the healthy cells, drug resistance, tumor relapse, the short half-life of employed drugs in the blood circulation, and the improper delivery of drugs toward the tumor site. The unique traits of stem cells (SCs) such as self-renewal, differentiation, tumor tropism, release of bioactive molecules, and immunosuppression have opened a new window for utilizing SCs as a novel tool in cancer treatment. In this regard, engineered SCs can secrete anti-cancer proteins or express enzymes used in suicide gene therapy which locally induce apoptosis in neoplastic cells via the bystander effect. These cells also stand as proper candidates to serve as careers for drug-loaded nanoparticles or to play suitable hosts for oncolytic viruses. Moreover, they harbor great potential to be employed in immunotherapy and combination therapy. However, tactful strategies should be devised to allow easier transplantation and protection of SCs from in vivo immune responses. In spite of the great hope concerning SCs application in cancer therapy, there are shortcomings and challenges to be addressed. This review tends to elaborate on recent advances on the various applications of SCs in cancer therapy and existing challenges in this regard.

scholarly journals A Systematic Review of the Genotoxicity and Antigenotoxicity of Biologically Synthesized Metallic Nanomaterials: Are Green Nanoparticles Safe Enough for Clinical Marketing?

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 439 ◽  
Author(s):  
Hamed Barabadi ◽  
Masoud Najafi ◽  
Hadi Samadian ◽  
Asaad Azarnezhad ◽  
Hossein Vahidi ◽  
...  
Keyword(s):  
Metallic Nanoparticles ◽  
Cancer Cell Line ◽  
Ag Nps ◽  
In Vivo Models ◽  
Biological Source ◽  
Metallic Nanomaterials ◽  
Biomedical Potential ◽  
Mcf 7

Background and objectives: Although studies have elucidated the significant biomedical potential of biogenic metallic nanoparticles (MNPs), it is very important to explore the hazards associated with the use of biogenic MNPs. Evidence indicates that genetic toxicity causes mutation, carcinogenesis, and cell death. Materials and Methods: Therefore, we systematically review original studies that investigated the genotoxic effect of biologically synthesized MNPs via in vitro and in vivo models. Articles were systematically collected by screening the literature published online in the following databases; Cochrane, Web of Science, PubMed, Scopus, Science Direct, ProQuest, and EBSCO. Results: Most of the studies were carried out on the MCF-7 cancer cell line and phytosynthesis was the general approach to MNP preparation in all studies. Fungi were the second most predominant resource applied for MNP synthesis. A total of 80.57% of the studies synthesized biogenic MNPs with sizes below 50 nm. The genotoxicity of Ag, Au, ZnO, TiO2, Se, Cu, Pt, Zn, Ag-Au, CdS, Fe3O4, Tb2O3, and Si-Ag NPs was evaluated. AgNPs, prepared in 68.79% of studies, and AuNPs, prepared in 12.76%, were the two most predominant biogenic MNPs synthesized and evaluated in the included articles. Conclusions: Although several studies reported the antigenotoxic influence of biogenic MNPs, most of them reported biogenic MNP genotoxicity at specific concentrations and with a dose or time dependence. To the best of our knowledge, this is the first study to systematically evaluate the genotoxicity of biologically synthesized MNPs and provide a valuable summary of genotoxicity data. In conclusion, our study implied that the genotoxicity of biologically synthesized MNPs varies case-by-case and highly dependent on the synthesis parameters, biological source, applied assay, etc. The gathered data are required for the translation of these nanoproducts from research laboratories to the clinical market.

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