scholarly journals Recent Developments in Nanoparticle-Based siRNA Delivery for Cancer Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Jong-Min Lee ◽  
Tae-Jong Yoon ◽  
Young-Seok Cho
Keyword(s):  
Cancer Therapy ◽  
Therapeutic Potential ◽  
Sirna Delivery ◽  
Molecular Therapy ◽  
Specific Gene ◽  
Regulation Mechanism ◽  
Rna Molecules ◽  
Effective Delivery ◽  
Recent Developments

RNA interference (RNAi) is a gene regulation mechanism initiated by RNA molecules that enables sequence-specific gene silencing by promoting degradation of specific mRNAs. Molecular therapy using small interfering RNA (siRNA) has shown great therapeutic potential for diseases caused by abnormal gene overexpression or mutation. The major challenges to application of siRNA therapeutics include the stability and effective delivery of siRNAin vivo. Important progress in nanotechnology has led to the development of efficient siRNA delivery systems. In this review, the authors discuss recent advances in nanoparticle-mediated siRNA delivery and the application of siRNA in clinical trials for cancer therapy. This review will also offer perspectives on future applications of siRNA therapeutics.

scholarly journals Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo

2019 ◽  
Vol 20 (24) ◽  
pp. 6123
Author(s):  
Changhao Cui ◽  
Shin Enosawa ◽  
Hitomi Matsunari ◽  
Hiroshi Nagashima ◽  
Akihiro Umezawa
Keyword(s):  
Therapeutic Potential ◽  
Parenchymal Cell ◽  
Severe Combined Immunodeficiency ◽  
Therapeutic Benefit ◽  
Human Albumin ◽  
Ammonia Removal ◽  
Mitogen Activated Protein Kinase ◽  
Specific Gene

To improve the therapeutic potential of hepatocyte transplantation, the effects of the mitogen-activated protein kinase kinase 4 (MKK4) inhibitor, myricetin (3,3′,4′,5,5′,7-hexahydroxylflavone) were examined using porcine and human hepatocytes in vitro and in vivo. Hepatocytes were cultured, showing the typical morphology of hepatic parenchymal cell under 1–10 µmol/L of myricetin, keeping hepatocyte specific gene expression, and ammonia removal activity. After injecting the hepatocytes into neonatal Severe combined immunodeficiency (SCID) mouse livers, cell colony formation was found at 10–15 weeks after transplantation. The human albumin levels in the sera of engrafted mice were significantly higher in the recipients of myricetin-treated cells than non-treated cells, corresponding to the size of the colonies. In terms of therapeutic efficacy, the injection of myricetin-treated hepatocytes significantly prolonged the survival of ornithine transcarbamylase-deficient SCID mice from 32 days (non-transplant control) to 54 days. Biochemically, the phosphorylation of MKK4 was inhibited in the myricetin-treated hepatocytes. These findings suggest that myricetin has a potentially therapeutic benefit that regulates hepatocyte function and survival, thereby treating liver failure.

In Vivo Dendritic Cell-specific Gene Silencing Using a Novel and Selective siRNA Delivery Method to Induce Immune Modulation

2007 ◽  
Vol 123 ◽  
pp. S64
Author(s):  
Costin Vladau ◽  
Dong Chen ◽  
Motohiko Suzuki ◽  
Xusheng Zhang ◽  
Xiufen Zheng ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Gene Silencing ◽  
Immune Modulation ◽  
Sirna Delivery ◽  
Specific Gene ◽  
Delivery Method

scholarly journals Optical imaging-guided cancer therapy with fluorescent nanoparticles

2009 ◽  
Vol 7 (42) ◽  
pp. 3-18 ◽  
Author(s):  
Shan Jiang ◽  
Muthu Kumara Gnanasammandhan ◽  
Yong Zhang
Keyword(s):  
Cancer Therapy ◽  
Optical Imaging ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Fluorescent Nanoparticles ◽  
Highly Sensitive ◽  
Imaging Probes ◽  
Recent Developments

The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy.

scholarly journals PD-L1 siRNA Theranostics With a Dextran Nanoparticle Highlights the Importance of Nanoparticle Delivery for Effective Tumor PD-L1 Downregulation

2021 ◽  
Vol 10 ◽  
Author(s):  
Jesus Pacheco-Torres ◽  
Marie-France Penet ◽  
Balaji Krishnamachary ◽  
Yelena Mironchik ◽  
Zhihang Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Checkpoint Inhibitors ◽  
Immunoblot Analysis ◽  
Immune Checkpoints ◽  
Specific Gene ◽  
Nanoparticle Delivery ◽  
Normal Tissues ◽  
Effective Delivery ◽  
20 Nm

PurposeThe inhibition of immune checkpoints such as programmed cell death ligand-1 (PD-L1/CD274) with antibodies is providing novel opportunities to expose cancer cells to the immune system. Antibody based checkpoint blockade can, however, result in serious autoimmune complications because normal tissues also express immune checkpoints. As sequence-specific gene-silencing agents, the availability of siRNA has significantly expanded the specificity and range of “druggable” targets making them promising agents for precision medicine in cancer. Here, we have demonstrated the ability of a novel biodegradable dextran based theranostic nanoparticle (NP) to deliver siRNA downregulating PD-L1 in tumors. Optical imaging highlighted the importance of NP delivery and accumulation in tumors to achieve effective downregulation with siRNA NPs, and demonstrated low delivery and accumulation in several PD-L1 expressing normal tissues.MethodsThe dextran scaffold was functionalized with small molecules containing amine groups through acetal bonds. The NP was decorated with a Cy5.5 NIR probe allowing visualization of NP delivery, accumulation, and biodistribution. MDA-MB-231 triple negative human breast cancer cells were inoculated orthotopically or subcutaneously to achieve differences in vascular delivery in the tumors. Molecular characterization of PD-L1 mRNA and protein expression in cancer cells and tumors was performed with qRT-PCR and immunoblot analysis.ResultsThe PD-L1 siRNA dextran NPs effectively downregulated PD-L1 in MDA-MB-231 cells. We identified a significant correlation between NP delivery and accumulation, and the extent of PD-L1 downregulation, with in vivo imaging. The size of the NP of ~ 20 nm allowed delivery through leaky tumor vasculature but not through the vasculature of high PD-L1 expressing normal tissue such as the spleen and lungs.ConclusionsHere we have demonstrated, for the first time, the feasibility of downregulating PD-L1 in tumors using siRNA delivered with a biodegradable dextran polymer that was decorated with an imaging reporter. Our data demonstrate the importance of tumor NP delivery and accumulation in achieving effective downregulation, highlighting the importance of imaging in siRNA NP delivery. Effective delivery of these siRNA carrying NPs in the tumor but not in normal tissues may mitigate some of the side-effects of immune checkpoint inhibitors by sparing PD-L1 inhibition in these tissues.

scholarly journals The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Inherited Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Sameh A. Abdelnour ◽  
Long Xie ◽  
Abdallah A. Hassanin ◽  
Erwei Zuo ◽  
Yangqing Lu
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Genetic Diseases ◽  
Patient Specific ◽  
Innovative Technology ◽  
Rna Molecules ◽  
Inherited Diseases ◽  
Genomic Editing

Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising innovative technology for genomic editing that offers scientists the chance to edit DNA structures and change gene function. It has several possible uses consisting of editing inherited deficiencies, treating, and reducing the spread of disorders. Recently, reports have demonstrated the creation of synthetic RNA molecules and supplying them alongside Cas9 into genome of eukaryotes, since distinct specific regions of the genome can be manipulated and targeted. The therapeutic potential of CRISPR/Cas9 technology is great, especially in gene therapy, in which a patient-specific mutation is genetically edited, or in the treating of human disorders that are untreatable with traditional treatments. This review focused on numerous, in vivo, in vitro, and ex vivo uses of the CRISPR/Cas9 technology in human inherited diseases, discovering the capability of this versatile in medicine and examining some of the main limitations for its upcoming use in patients. In addition to introducing a brief impression of the biology of the CRISPR/Cas9 scheme and its mechanisms, we presented the utmost recent progress in the uses of CRISPR/Cas9 technology in editing and treating of human genetic diseases.

scholarly journals Concepts in in vivo siRNA delivery for cancer therapy

2009 ◽  
Vol 220 (2) ◽  
pp. 285-291 ◽  
Author(s):  
Christopher S. Gondi ◽  
Jasti S. Rao
Keyword(s):  
Cancer Therapy ◽  
Sirna Delivery

scholarly journals Nanobody Conjugates for Targeted Cancer Therapy and Imaging

2021 ◽  
Vol 20 ◽  
pp. 153303382110101
Author(s):  
Wei Kang ◽  
Chuanfeng Ding ◽  
Danni Zheng ◽  
Xiao Ma ◽  
Lun Yi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Full Potential ◽  
Targeted Cancer Therapy ◽  
Large Size ◽  
Naturally Occurring ◽  
Recent Developments ◽  
Potential Applications ◽  
Conventional Antibody ◽  
Insight Into

Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivo pharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.

scholarly journals MicroRNA-based therapeutics in central nervous system injuries

2018 ◽  
Vol 38 (7) ◽  
pp. 1125-1148 ◽  
Author(s):  
Ping Sun ◽  
Da Zhi Liu ◽  
Glen C Jickling ◽  
Frank R Sharp ◽  
Ke-Jie Yin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Time Windows ◽  
Pharmacological Agents ◽  
Rna Molecules ◽  
Cord Injury ◽  
Effective Delivery ◽  
Underlying Mechanisms

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood–brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

MiR490's diagnostic capacity was demonstrated in various cancer kinds and diseases, adding to its clinical value

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Molecular Therapy ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Clinical Value ◽  
Cancer Types ◽  
Diagnostic Capacity

This miR‐490 review first illustrates its association with various clinical malignancies and other diseases. Although in various malignancies miR‐490's activities, regulatory mechanisms and targets were revealed, its significance to other illnesses is beginning to be studied. Note that miR‐490 levels are regulated at different levels by transcription factors, epigenetic factors, and ncRNAs, revealing complicated interplay between these components. A system approach that incorporates miR‐490 and its regulatory components will surely help detect critical miR‐490 hub connections that might affect tumor initiation/progression. Furthermore, a number of pharmacological and environmental variables known to cause disease have also been shown to alter miR‐490 levels, showing miR‐490's significant pathogenesis involvement. The fact that miR‐490 levels are strictly regulated and abnormal miR‐490 levels are reported in many cancer types and diseases highlights miR‐490's significance in controlling cell homeostasis.Due to their increased stability, miRNAs are developed as diagnostic agents. MiR‐490's diagnostic capacity was demonstrated in various cancer kinds and diseases, adding to its clinical value. The potential of miR‐490 as a non-invasive biomarker might possibly be studied by measuring patient serum/saliva/urine levels in tissues or body fluids. Furthermore, miR‐490's demonstrated ability to stratify healthy tissue tumor samples may aid establishing molecular diagnostic tools. In most circumstances, miR‐490's association with improved prognosis is also fascinating. This extra clinical importance makes miR‐490 appropriate for molecular therapy. In most cancer types where miR‐490 has been functionally identified, miR‐490 has been found to be a miRNA tumor suppressor that inhibits several cancer hallmarks by directly controlling oncogenic targets and pathways. In practical practice, a therapy regime using miR‐490 tissue alteration based on rapidly evolving targeted delivery methods may be on the horizon. Nevertheless, further in vivo investigations must be conducted using genetically changed mice models. Although miR‐490 was not yet clinically examined for its therapeutic potential, in vitro and in vivo preclinical experiments revealed enormous promise in translating miR‐490 as a novel therapeutic target. miR‐490 appears as a novel candidate miRNA with significant cancer diagnosis and therapy with its prognostic and diagnostic capabilities. Therefore, miR‐490 might serve as a novel weapon in the current anti-cancer treatment arsenal.

Nanocarrier Mediated siRNA Delivery Targeting Stem Cell Differentiation

2020 ◽  
Vol 15 (2) ◽  
pp. 155-172 ◽  
Author(s):  
Fiona Fernandes ◽  
Pooja Kotharkar ◽  
Adrija Chakravorty ◽  
Meenal Kowshik ◽  
Indrani Talukdar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Viral Vectors ◽  
Therapeutic Potential ◽  
Transfection Efficiency ◽  
Polymeric Nanoparticles ◽  
Sirna Delivery ◽  
Stem Cell Differentiation

Stem cell-based regenerative medicine holds exceptional therapeutic potential and hence the development of efficient techniques to enhance control over the rate of differentiation has been the focus of active research. One of the strategies to achieve this involves delivering siRNA into stem cells and exploiting the RNA interference (RNAi) mechanism. Transport of siRNA across the cell membrane is a challenge due to its anionic property, especially in primary human cells and stem cells. Moreover, naked siRNA incites immune responses, may cause off-target effects, exhibits low stability and is easily degraded by endonucleases in the bloodstream. Although siRNA delivery using viral vectors and electroporation has been used in stem cells, these methods demonstrate low transfection efficiency, cytotoxicity, immunogenicity, events of integration and may involve laborious customization. With the advent of nanotechnology, nanocarriers which act as novel gene delivery vehicles designed to overcome the problems associated with safety and practicality are being developed. The various nanomaterials that are currently being explored and discussed in this review include liposomes, carbon nanotubes, quantum dots, protein and peptide nanocarriers, magnetic nanoparticles, polymeric nanoparticles, etc. These nanodelivery agents exhibit advantages such as low immunogenic response, biocompatibility, design flexibility allowing for surface modification and functionalization, and control over the surface topography for achieving the desired rate of siRNA delivery and improved gene knockdown efficiency. This review also includes discussion on siRNA co-delivery with imaging agents, plasmid DNA, drugs etc. to achieve combined diagnostic and enhanced therapeutic functionality, both for in vitro and in vivo applications.

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