Abstract:Recent findings in nanomedicine have revealed that carbon nanotubes (CNTs) can be used as potential drug carriers, therapeutic agents and diagnostics tools. Moreover, due to their ability to cross cellular membranes, their nanosize dimension, high surface area and relatively good biocompatibility, CNTs have also been employed as a novel gene delivery vector system. In our previous work, we functionalized CNTs with two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM). These compo… Show more
“…Therefore, the functionalization of PAMAM dendrimer with Rhodamine B dye allowed us to obtain a multifunctional system able not only to be monitored during the internalization into cells, but also to follow the delivery of miRNAs. This functionalization significantly improved the commercial system already assessed in our previous works 25 , 26 and proved that the functionalization did not alter significantly its transfection and toxicity properties. Figure 6 Fluorescence images of HeLa cells after treatments with Rho 1% -PAM solution alone ( A ) and complexed with FAM-mir-503 (4:1 w/w ratio) ( B ).…”
Section: Resultssupporting
confidence: 60%
“…A recent study from our group assessed the ability of PAMAM to bind effectively a ~70 nt oligonucleotide (oligo) mimicking a pre-miRNA (hsa-mir-503) for the delivery of non-coding RNAs into cells 25 . To assess the ability of PLA scaffold coated with Rho 1% -PAM to bind small nucleic acids (i.e., oligonucleotides, miRNA mimic, etc.…”
Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications.
“…Therefore, the functionalization of PAMAM dendrimer with Rhodamine B dye allowed us to obtain a multifunctional system able not only to be monitored during the internalization into cells, but also to follow the delivery of miRNAs. This functionalization significantly improved the commercial system already assessed in our previous works 25 , 26 and proved that the functionalization did not alter significantly its transfection and toxicity properties. Figure 6 Fluorescence images of HeLa cells after treatments with Rho 1% -PAM solution alone ( A ) and complexed with FAM-mir-503 (4:1 w/w ratio) ( B ).…”
Section: Resultssupporting
confidence: 60%
“…A recent study from our group assessed the ability of PAMAM to bind effectively a ~70 nt oligonucleotide (oligo) mimicking a pre-miRNA (hsa-mir-503) for the delivery of non-coding RNAs into cells 25 . To assess the ability of PLA scaffold coated with Rho 1% -PAM to bind small nucleic acids (i.e., oligonucleotides, miRNA mimic, etc.…”
Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications.
“…We have previously shown that PAMAM-CNTs at 50 µg/mL, equivalent to the dose used in the present study, have low cyto-toxicity 30,31 . Cellular viability of human umbilical vein endothelial cells (HUVECs) is not altered compared to controls in the presence of PAMAM-CNTs.…”
Section: Cellular Stress Gene Expression Is Not Increased By Pamam-cntsmentioning
In this study, the use of dendrimer-coated carbon nanotubes (CNTs) as a delivery vehicle for dsRNA was assessed in Tribolium castaneum. Exposure to low dosages of polyamidoamine dendrimer carbon nanotubes (PAMAM-CNTs) did not affect T. castaneum larval mortality. Expression of key apoptotic factors, Dronc (Tc12580), Dredd (Tcn-like, Tc014026) and Buffy, (Tcinhib apop1), which can act as toxicity indicators, were not altered in T. castaneum larvae following injection of PAMAM-CNTs. The level of knockdown of two target genes, α-tubulin and mitochondrial RNA polymerase (mtpol), were significantly increased when larvae were injected with double-stranded RNA bound to CNTs (PAMAM-CNT-dsRNA), compared to those injected with target dsRNA alone. PAMAM-CNTs were visualised in cellular vacuoles and in the cell nucleus. Increase occurrence of a blistered wing phenotype was found in a subset of PAMAM-CNT-dsRNA αtub injected larvae, relative to the level seen in larvae injected with naked dsRnA αtub alone. These results suggest that the use of functionalised CNTs for dsRNA delivery could increase the efficacy of RNA interference in insect pest species. RNA interference (RNAi) is a promising tool for the control of insect pests. Introduction of exogenous doublestranded RNA (dsRNA) is effective at triggering gene knockdown and associated phenotypes in many problem pest species such as the Western Corn Rootworm 1 , the Colorado potato beetle 2 and the Varroa mite 3. New developments in dsRNA delivery methods to crop pests, such as dsRNA expression in transgenic plants 4 and foliar application 5 , offer the possibility of dsRNA-based insecticides 6. Despite this promise, there is notable variation in RNAi response between insect species 7 , with some, such as many lepidopterans 8 , unable to mount a strong RNAi response to dsRNA. Ingestion of dsRNA can be a valid route for delivery, yet many insects secrete enzymes in their gut that breakdown dsRNA before the latter can elicit an effect on target gene transcripts 9-11. When dsRNA enters into the cytoplasm, it is generally very effective in mounting an RNAi response 12,13. However, the route to the cytoplasm can act as a barrier to effective RNAi, with stability and uptake of dsRNA within the insect thought to be the significant limiting factor 10,11,14,15. Therefore, the protection of dsRNA from degradation coupled with an efficient cellular uptake is key to RNAi success. The development of delivery vehicles or carriers that enable these two processes is now necessary to fully realise the potential for dsRNA as an effective control measure. Combining dsRNA with other substances that act as efficient carriers, such as chitosan 16,17 , perfluorocarbon nanoparticles 18-20 or ribonuceloparticles 21 , can stabilise dsRNA and increase the chances of successful gene knockdown. Encapsulation of dsRNA within carbon quantum dots 22 and liposomes 23,24 has also shown some promise in increasing efficacy in more challenging insect species. In the last decade, carbon nanotubes (CNTs) have emerg...
“…Carbon nanotubes (CNT) were used as another platform for binding PAMAM and PEI for delivering microRNAS (miRNAS) [ 83 ]. Different sizes of CNT were used, including biodimensional sheets (bucky papers (BP)) and the corresponding molecules, which are effective for transfection in different ways (BP, for example, can act as a ‘nanoneedle’ to pierce the cell).…”
Section: Biomedical Applicationsmentioning
confidence: 99%
“…Different sizes of CNT were used, including biodimensional sheets (bucky papers (BP)) and the corresponding molecules, which are effective for transfection in different ways (BP, for example, can act as a ‘nanoneedle’ to pierce the cell). The CNT strategy [ 83 ] was then be applied by Masotti and coworkers [ 84 ], employing PAMAM and PEI coated with CNT, which was conjugated with miR-503 oligonucleotides, aiming at the regulation of angiogenesis in endothelial cells. On the other hand, miR-503, whose target is named CDC25A, is overexpressed on diabetes mellitus, and also the gene that is responsible for endothelial cells proliferation [ 85 ].…”
Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.
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