scholarly journals Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3489
Author(s):  
Daniela Ferreira ◽  
David Fontinha ◽  
Catarina Martins ◽  
David Pires ◽  
Alexandra R. Fernandes ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Nucleic Acids ◽  
Treatment Strategies ◽  
Cancer Therapeutics ◽  
Delivery Systems ◽  
Nucleic Acid Delivery ◽  
In Vivo Models ◽  
Or Gene

Cancer remains a complex medical challenge and one of the leading causes of death worldwide. Nanomedicines have been proposed as innovative platforms to tackle these complex diseases, where the combination of several treatment strategies might enhance therapy success. Among these nanomedicines, nanoparticle mediated delivery of nucleic acids has been put forward as key instrument to modulate gene expression, be it targeted gene silencing, interference RNA mechanisms and/or gene edition. These novel delivery systems have strongly relied on nanoparticles and, in particular, gold nanoparticles (AuNPs) have paved the way for efficient delivery systems due to the possibility to fine-tune their size, shape and surface properties, coupled to the ease of functionalization with different biomolecules. Herein, we shall address the different molecular tools for modulation of expression of oncogenes and tumor suppressor genes and discuss the state-of-the-art of AuNP functionalization for nucleic acid delivery both in vitro and in vivo models. Furthermore, we shall highlight the clinical applications of these spherical AuNP based conjugates for gene delivery, current challenges, and future perspectives in nanomedicine.

scholarly journals Surface-Initiated Atom Transfer Polymerized Anionic Corona on Gold Nanoparticles for Anti-Cancer Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 261
Author(s):  
Wei Mao ◽  
Sol Lee ◽  
Ji Un Shin ◽  
Hyuk Sang Yoo
Keyword(s):  
Gold Nanoparticles ◽  
Transfection Efficiency ◽  
Cancer Therapeutics ◽  
Atom Transfer ◽  
Layer By Layer ◽  
Dependent Manner ◽  
Metallic Particles ◽  
Anti Cancer

Surface initiated atom transfer radical polymerization (SI-ATRP) documented a simple but efficient technique to grow a dense polymer layer on any surface. Gold nanoparticles (AuNPs) give a broad surface to immobilize sulfhyryl group-containing initiators for SI-ATRP; in addition, AuNPs are the major nanoparticulate carriers for delivery of anti-cancer therapeutics, since they are biocompatible and bioinert. In this work, AuNPs with a disulfide initiator were polymerized with sulfoethyl methacrylate by SI-ATRP to decorate the particles with anionic corona, and branched polyethyeleneimine (PEI) and siRNA were sequentially layered onto the anionic corona of AuNP by electrostatic interaction. The in vitro anti-cancer effect confirmed that AuNP with anionic corona showed higher degrees of apoptosis as well as suppression of the oncogene expression in a siRNA dose-dependent manner. The in vivo study of tumor-bearing nude mice revealed that mice treated with c-Myc siRNA-incorporated AuNPs showed dramatically decreased tumor size in comparison to those with free siRNA for 4 weeks. Furthermore, histological examination and gene expression study revealed that the decorated AuNP significantly suppressed c-Myc expression. Thus, we envision that the layer-by-layer assembly on the anionic brushes can be potentially used to incorporate nucleic acids onto metallic particles with high transfection efficiency.

scholarly journals Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gold Nanoparticles ◽  
Gene Silencing ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Ovarian Cancer Cells ◽  
Interfering Rna

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.

Somatic Mutational Landscape of AML with Inv(16) and t(8;21) Identifies Two Distinct Patterns in Relapse Tumors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2362-2362
Author(s):  
Raman B. Sood ◽  
Nancy F Hansen ◽  
Frank X Donovan ◽  
Blake Carrington ◽  
Baishali Maskeri ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Clonal Evolution ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Driver Gene ◽  
Intrinsic Resistance ◽  
Driver Genes ◽  
In Vivo Models

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with a wide prognostic spectrum ranging from poor to good depending upon the underlying mutations and/or cytogenetic abnormalities. Although AMLs with inv(16)/t(16:16) or t(8,21), collectively referred to as core binding factor leukemias (CBF-AMLs), are classified as prognostically favorable, such patients often succumb to their disease following relapse after an initial response to cytarabine/anthracyclin-based treatment regimens. Thus, to develop successful treatment strategies, it is critical to understand the mechanisms leading to disease relapse and target them with novel therapeutic approaches. To pursue this goal, we applied genomic approaches (whole exome sequencing and single nucleotide polymorphism arrays) on DNA from samples collected at sequential time points (i.e., diagnosis, complete remission and relapse) in seven patients with inv(16) and six patients with t(8;21). We identified mutations in several previously identified AML driver genes, such as KIT, FLT3, DNMT3A, EZH2, SMC1A, SMC3, WT1 and NRAS. Three relapse samples showed mosaicism for monosomy/disomy of the region of chromosome 3 containing GATA2. Overall, our data revealed two distinct profiles that support different mechanisms of relapse: 1) diagnosis and relapse blasts harbor the same driver gene mutations, indicating the intrinsic resistance of the major clones present at diagnosis to treatment regimen used; 2) diagnosis and relapse tumors have different driver gene mutations, indicating disease clonal evolution possibly through treatment selective pressure. Furthermore, our data has identified previously unreported putative driver genes for AML. Among these, we identified same somatic variant (R222G) in DHX15, an RNA helicase involved in splicing, in two patients at diagnosis. The variant was also detected at relapse in one of these patients. Functional validation of the mechanistic roles of wild type and mutated DHX15 in hematopoiesis and leukemogenesis, respectively, is ongoing in in vitro and in vivo models. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Hali Bordelon ◽  
Alexandru S. Biris ◽  
Cristina M. Sabliov ◽  
W. Todd Monroe
Keyword(s):  
Nucleic Acids ◽  
Plasmid Dna ◽  
Genetic Manipulation ◽  
Chitosan Nanoparticles ◽  
Complex Surface ◽  
Surface Enhanced Raman Spectroscopy ◽  
Nucleic Acid Delivery ◽  
Label Free

Poly(D,L-lactide-co-glycolide-) (PLGA-)chitosan nanoparticles are becoming an increasingly common choice for the delivery of nucleic acids to cells for various genetic manipulation techniques. These particles are biocompatible, with tunable size and surface properties, possessing an overall positive charge that promotes complex formation with negatively charged nucleic acids. This study examines properties of the PLGA-chitosan nanoparticle/plasmid DNA complex after formation. Specifically, the study aims to determine the optimal ratio of plasmid DNA:nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within these complexes. Such characterization will be necessary for the adoption of these formulations in a clinical setting. The ability of PLGA-chitosan nanoparticles to form complexes with pDNA was evaluated by using the fluorescent intercalating due OliGreen to label free plasmid DNA. By monitoring the fluorescence at different plasmid: nanoparticle ratios, the ideal plasmid:nanoparticle ration for complete complexation of plasmid was determined to be 1:50. Surface-Enhanced Raman Spectroscopy and gel digest studies suggested that even at these optimal complexation ratios, a portion of the plasmid DNA was located on the outer complex surface. This knowledge will facilitate future investigations into the functionality of the systemin vitroandin vivo.

Gold Nanoparticles as Targeted Delivery Systems and Theranostic Agents in Cancer Therapy

2019 ◽  
Vol 26 (35) ◽  
pp. 6493-6513 ◽  
Author(s):  
Alexandra Mioc ◽  
Marius Mioc ◽  
Roxana Ghiulai ◽  
Mirela Voicu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Theranostic Agents ◽  
Targeted Delivery Systems

Cancer is still a leading cause of death worldwide, while most chemotherapies induce nonselective toxicity and severe systemic side effects. To address these problems, targeted nanoscience is an emerging field that promises to benefit cancer patients. Gold nanoparticles are nowadays in the spotlight due to their many well-established advantages. Gold nanoparticles are easily synthesizable in various shapes and sizes by a continuously developing set of means, including chemical, physical or eco-friendly biological methods. This review presents gold nanoparticles as versatile therapeutic agents playing many roles, such as targeted delivery systems (anticancer agents, nucleic acids, biological proteins, vaccines), theranostics and agents in photothermal therapy. They have also been outlined to bring great contributions in the bioimaging field such as radiotherapy, magnetic resonance angiography and photoacoustic imaging. Nevertheless, gold nanoparticles are therapeutic agents demonstrating its in vitro anti-angiogenic, anti-proliferative and pro-apoptotic effects on various cell lines, such as human cervix, human breast, human lung, human prostate and murine melanoma cancer cells. In vivo studies have pointed out data regarding the bioaccumulation and cytotoxicity of gold nanoparticles, but it has been emphasized that size, dose, surface charge, sex and especially administration routes are very important variables.

scholarly journals RIT1: A Novel Biomarker in Glioblastoma

2020 ◽  
Author(s):  
Athar Khalil ◽  
Georges Nemer
Keyword(s):  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Treatment Strategies ◽  
Poor Overall Survival ◽  
In Vivo Models ◽  
Proliferation And Differentiation ◽  
Ras Family ◽  
Upregulated Genes

AbstractGlioblastoma is the most common type of malignant brain tumors and the most feared cancer among adults. Its high invasiveness and the lack of successful therapies are responsible for the poor prognosis among these patients. A comprehensive understanding for the early molecular mechanisms in glioblastoma would definitely enhance its diagnosis and treatment strategies. Based on in vitro and in vivo models, it was recently postulated that the deregulated expression of key genes that are known to be involved in early neurogenesis could be the instigator of brain tumorigenesis. RIT1 (Ras Like Without CAAX 1) which encodes an unusual “orphan” GTPase protein belongs to this category of critical genes involved in controlling sequential proliferation and differentiation of adult hippocampal neural progenitor cells. As such, we surveyed RIT1 expression and its potential role in glioblastoma by in-silico means. Our results revealed a significant and progressive upregulation of RIT1 expression in various publicly available datasets. RIT1 expression ranked among the top upregulated genes in glioblastoma cohorts and correlated with poor overall survival. Genetic and epigenetic analysis of RIT1 didn’t reveal significant aberrations that could underlie its deregulated expression. Moreover, our results pointed on RIT1 transcriptional activity that could be significantly controlled by STAT3, one of the main players in the onset of glioblastoma. In conclusion, our results are the first proof for the role of RIT1 as an oncogene in glioblastoma paving the way for its potential use as a biomarker and therapeutic target as is the case of the other members in the RAS family.

scholarly journals Developing preclinical models of neuroblastoma: driving therapeutic testing

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Kimberly J. Ornell ◽  
Jeannine M. Coburn
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapeutics ◽  
Tumor Stroma ◽  
In Vitro Models ◽  
Preclinical Models ◽  
In Vivo Models ◽  
Therapeutic Development ◽  
Potential Applications

AbstractDespite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with high-risk NB exhibit a survival rate of 40–50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.

scholarly journals Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1180
Author(s):  
Giovanna Rassu ◽  
Milena Sorrenti ◽  
Laura Catenacci ◽  
Barbara Pavan ◽  
Luca Ferraro ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Biological Activities ◽  
Detailed Examination ◽  
Delivery Systems ◽  
Nasal Drug Delivery ◽  
In Vivo Models ◽  
Nasal Application

Cyclodextrins (CDs) are oligosaccharides widely used in the pharmaceutical field. In this review, a detailed examination of the literature of the last two decades has been made to understand the role of CDs in nasal drug delivery systems. In nasal formulations, CDs are used as pharmaceutical excipients, as solubilizers and absorption promoters, and as active ingredients due to their several biological activities (antiviral, antiparasitic, anti-atherosclerotic, and neuroprotective). The use of CDs in nasal formulations allowed obtaining versatile drug delivery systems intended for local and systemic effects, as well as for nose-to-brain transport of drugs. In vitro and in vivo models currently employed are suitable to analyze the effects of CDs in nasal formulations. Therefore, CDs are versatile pharmaceutical materials, and due to the continual synthesis of new CDs derivatives, the research on the new nasal applications is an interesting field evolving in the coming years, to which Italian research will still contribute.

scholarly journals Hydrogels as Drug Delivery Systems: A Review of Current Characterization and Evaluation Techniques

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1188
Author(s):  
Margaux Vigata ◽  
Christoph Meinert ◽  
Dietmar W. Hutmacher ◽  
Nathalie Bock
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Analytical Techniques ◽  
Delivery Systems ◽  
Local Drug Delivery ◽  
Experimental Conditions ◽  
In Vivo Models

Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.

scholarly journals Naringenin Nano-Delivery Systems and Their Therapeutic Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 291
Author(s):  
Mohammed Bhia ◽  
Mahzad Motallebi ◽  
Banafshe Abadi ◽  
Atefeh Zarepour ◽  
Miguel Pereira-Silva ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Delivery Systems ◽  
In Vivo Models ◽  
Wide Range

Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.

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