scholarly journals Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells

Oncotarget ◽  
2015 ◽  
Vol 6 (28) ◽  
pp. 26177-26191 ◽  
Author(s):  
Jun Li ◽  
Shengnan Li ◽  
Songyun Xia ◽  
Jinfeng Feng ◽  
Xuedi Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Targeted Delivery ◽  
Transfection Efficiency ◽  
Self Assembling

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

2020 ◽  
Vol 10 ◽  
Author(s):  
Krishna Champaneria ◽  
Prajesh Prajapati
Keyword(s):  
Adverse Effects ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Blood Circulation ◽  
Review Paper ◽  
Tumor Therapy ◽  
Conventional Chemotherapy ◽  
Targeting Delivery ◽  
Tumor Accumulation ◽  
Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

scholarly journals Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Federica Palombarini ◽  
Silvia Masciarelli ◽  
Alessio Incocciati ◽  
Francesca Liccardo ◽  
Elisa Di Fabio ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Electrostatic Interactions ◽  
Archaeoglobus Fulgidus ◽  
Leukemia Cells ◽  
Cellular Delivery ◽  
Self Assembling ◽  
Wide Range ◽  
Hybrid Nanoparticle

Abstract Background In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. Graphic abstract

scholarly journals Bone tumor-targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells

2020 ◽  
pp. 100088
Author(s):  
Robin A. Nadar ◽  
Gerben M. Franssen ◽  
Natasja W.M. Van Dijk ◽  
Karlijn Codee-van der Schilden ◽  
Mirjam de Weijert ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Bone Tumor ◽  
Targeted Delivery ◽  
Metastatic Tumor

scholarly journals Photosensitizer Chlorin e6 Internalization into Tumor Cells in Phospholipid Nanoparticles Conjugated with Peptide Containing the NGR Sequence

2018 ◽  
Vol 1 (4) ◽  
pp. e00063 ◽  
Author(s):  
V.N. Prozorovskiy ◽  
L.V. Kostryukova ◽  
E.I. Korotkevich ◽  
T.I. Torkhovskaya ◽  
G.E. Morozevich ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Amino Acid ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Aminopeptidase N ◽  
Chlorin E6 ◽  
Phospholipid Nanoparticles ◽  
Chlorine E6 ◽  
Targeting Peptide ◽  
Mcf 7

The possibility of increased internalization of the photosensitizer chlorin e6 in tumor cells was investigatedusing soy phosphatidylcholine nanoparticles 20-30 nm with or without attached peptide containing Asn-Gly-Arg (NGR) motif was studied. This amino acid sequence exhibits affinity to aminopeptidase N (CD13), wich is overexpressed in a number of tumor cells and vessels. Nanoparticles with chlorin e6 were prepared with added of distearoylphosphatidylcholine (DSPE) conjugated through PEG with a hexapeptide containing the NGR sequence, and then were incubated with tumor cells НерG2 and MCF-7. Chlorin e6 accumulation in СD13-negative cells (MCF-7) did not depend on the presence of peptide NGR in nanoparticles. However, for НерG2 cells a twofold increase of chlorine e6 internalization was observed as compared with the same particles without NGR. Differences in the response of these two cell lines, differed in expression of aminopeptidase N (APN), suggest the possibility of this protein using for targeted delivery. The prospectivity of usage of phospholipids nanoparticles conjugated with targeting peptide for photodynamic therapy is discussed, taking into account possible variation of APN expression, inherent for many solid tumors.

scholarly journals Electrospray preparation of biocompatible lactide–glycolide copolymer capsules with incorporation of interferon

2019 ◽  
Vol 484 (6) ◽  
pp. 703-708
Author(s):  
I. A. Khlusov ◽  
E. V. Kibler ◽  
V. L. Kudryavtseva ◽  
S. I. Tverdokhlebov ◽  
E. N. Bolbasov ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Structural Integrity ◽  
Environmental Safety ◽  
Biological Molecules ◽  
Confocal Laser ◽  
Human Interferon ◽  
First Time ◽  
Scanning Electron

The electrospray method was used for the first time to prepare polymeric capsules from bioresorbable dl-lactide and glycolide copolymer loaded with biological molecules from the cell secretome and, in particular, human interferon a-2b (IFN a-2b). The obtained nearly spherical submicron capsules were studied by scanning electron and confocal laser microscopy. The capsules retain the structural integrity and the cytotoxic activity of IFN a-2b towards tumor cells. The electrospray method is distinguished by high adaptability and environmental safety and is suitable for manufacture of a broad range of materials with different composition and morphology promising for the targeted delivery of drugs and biological molecules.

Targeted Delivery and Redox Activity of Folic Acid-Functionalized Nanoceria in Tumor Cells

2018 ◽  
Vol 15 (3) ◽  
pp. 994-1004 ◽  
Author(s):  
James A. Vassie ◽  
John M. Whitelock ◽  
Megan S. Lord
Keyword(s):  
Folic Acid ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Redox Activity

scholarly journals 2219

2017 ◽  
Vol 1 (S1) ◽  
pp. 59-59
Author(s):  
Shaheen Kurani ◽  
Nicolas Madigan ◽  
Karl Clark ◽  
Stephen Ekker ◽  
Nathan Staff ◽  
...  
Keyword(s):  
Cell Survival ◽  
Targeted Delivery ◽  
Transfection Efficiency ◽  
Current Treatment ◽  
Safe Harbor ◽  
Systemic Delivery ◽  
Transcription Activator ◽  
Field Methods ◽  
A Cell ◽  
The Central Nervous System

OBJECTIVES/SPECIFIC AIMS: The current treatment for amyotrophic lateral sclerosis (ALS) includes systemic delivery of neurotrophic factors (NTFs). Although this approach may seem theoretically sound, NTF efficacy within the central nervous system (CNS) is largely limited by the blood-brain barrier. Thus, a cell-based approach, which allows for targeted delivery of molecular therapies locally from the CNS, could lead to a paradigm shift in the field. METHODS/STUDY POPULATION: The Windebank and Staff group at Mayo Clinic completed a Phase I dose-escalation safety trial of autologous, adipose-derived mesenchymal stem cells (adMSCs) in an effort to move toward personalized medical treatment of ALS. The adMSCs were injected into the intrathecal space by lumbar puncture in 27 patients and the results showed an excellent safety profile across a range of doses. The team is moving forward with this idea by using gene-editing technology to develop clinical-grade, genetically modified autologous MSCs. The patient-derived adMSCs are modified at defined “safe-harbor” regions of the human genome through transcription activator-like effector nuclease (TALEN) technology. RESULTS/ANTICIPATED RESULTS: Our results show that electroporating adMSCs with plasmid DNA leads to efficient GFP or TALEN transgene expression, but yields low cell survival and a low rate of genetic modification. DISCUSSION/SIGNIFICANCE OF IMPACT: It can be concluded that: (1) TALEN technology may be used to target safe harbor loci for gene integration to produce therapeutic adMSC for ALS. (2) Primary barriers to adMSC modification are inefficient TALEN and donor template uptake, low cutting efficiency, and poor cell survival after electroporation. Future directions include optimizing the protocol to obtain 48 base pairs in the homology arms and increasing transfection efficiency.

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