“…Moreover siRNA, when used without adding of any transfection agent, works better; it decreases the GFP fluorescence signal to 75 percent of the starting signal, which further confirms our hypothesis. An attractive option for future biological studies of the JK39 fullerene nanomaterial could be to test the photocleavage of the JK39-siRNA stable complex based on the irradiation of cells with blue/green light (glycofullerenes are photosensitizers) and the generation of ROS, which led to good results for the C 60 -Dex-NH 2 fullerene and the upconversion nanomaterials that were used as the siRNA transfection agents 13 , 50 . Figure 4 The efficiency of the siRNA transfer in vitro with the engineered fullerene nanomaterials HexakisaminoC 60 and JK39 and the resulting EGFP silencing in a prostate cancer model (DU145 cells that had been transfected with the plasmid encoding EGFP).…”
Section: Resultsmentioning
confidence: 99%
“…Moreover, it has been proven that TPFE is non-toxic and is effective for lung-targeted in vivo siRNA delivery, which is based on the formation of the micrometer-sized TPFE–siRNA–serum protein complexes, which could be a stabilization factor for relatively unstable siRNA under physiological conditions 12 . Studies performed by Wang et al described a fullerene-ethylenediamine modified dextran hybrid (C 60 -Dex-NH 2 ) as an efficient siRNA transfection agent when they evaluated it in the human breast cancer cell line MDA-MB-231, which could be photo-activated and could destroy the endo-lysosomal membranes via a controllable generation of ROS 13 . Simultaneously, the interactions of carbon nanomaterials with biological fluids are crucial factors that determine their cellular fate and further tissue targeting 14 , 15 .…”
This paper presents two water-soluble fullerene nanomaterials (HexakisaminoC60 and monoglucosamineC60, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel–Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as d-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI–MS and 13C-NMR analyses of JK39 confirmed its high Th symmetry, while X-ray photoelectron spectroscopy revealed the presence of nitrogen and oxygen-containing C–O or C–N bonds. The efficiency of both fullerenes as siRNA vehicles was tested in vitro using the prostate cancer cell line DU145 expressing the GFP protein. The HexakisaminoC60 fullerene was an efficient siRNA transfection agent, and decreased the GFP fluorescence signal significantly in the DU145 cells. Surprisingly, the glycofullerene JK39 was inactive in the transfection experiments, probably due to its high zeta potential and the formation of an extremely stable complex with siRNA.
“…Moreover siRNA, when used without adding of any transfection agent, works better; it decreases the GFP fluorescence signal to 75 percent of the starting signal, which further confirms our hypothesis. An attractive option for future biological studies of the JK39 fullerene nanomaterial could be to test the photocleavage of the JK39-siRNA stable complex based on the irradiation of cells with blue/green light (glycofullerenes are photosensitizers) and the generation of ROS, which led to good results for the C 60 -Dex-NH 2 fullerene and the upconversion nanomaterials that were used as the siRNA transfection agents 13 , 50 . Figure 4 The efficiency of the siRNA transfer in vitro with the engineered fullerene nanomaterials HexakisaminoC 60 and JK39 and the resulting EGFP silencing in a prostate cancer model (DU145 cells that had been transfected with the plasmid encoding EGFP).…”
Section: Resultsmentioning
confidence: 99%
“…Moreover, it has been proven that TPFE is non-toxic and is effective for lung-targeted in vivo siRNA delivery, which is based on the formation of the micrometer-sized TPFE–siRNA–serum protein complexes, which could be a stabilization factor for relatively unstable siRNA under physiological conditions 12 . Studies performed by Wang et al described a fullerene-ethylenediamine modified dextran hybrid (C 60 -Dex-NH 2 ) as an efficient siRNA transfection agent when they evaluated it in the human breast cancer cell line MDA-MB-231, which could be photo-activated and could destroy the endo-lysosomal membranes via a controllable generation of ROS 13 . Simultaneously, the interactions of carbon nanomaterials with biological fluids are crucial factors that determine their cellular fate and further tissue targeting 14 , 15 .…”
This paper presents two water-soluble fullerene nanomaterials (HexakisaminoC60 and monoglucosamineC60, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel–Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as d-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI–MS and 13C-NMR analyses of JK39 confirmed its high Th symmetry, while X-ray photoelectron spectroscopy revealed the presence of nitrogen and oxygen-containing C–O or C–N bonds. The efficiency of both fullerenes as siRNA vehicles was tested in vitro using the prostate cancer cell line DU145 expressing the GFP protein. The HexakisaminoC60 fullerene was an efficient siRNA transfection agent, and decreased the GFP fluorescence signal significantly in the DU145 cells. Surprisingly, the glycofullerene JK39 was inactive in the transfection experiments, probably due to its high zeta potential and the formation of an extremely stable complex with siRNA.
“…[9][10][11][12][13] Further developmentso fa ccurates ynthetic manipulation [14] and (bio)orthogonal click-chemistry methodologies [15][16][17] have enabled the access to single-isomer,n anometric-sized molecules having ap ersistent topology and ap re-oriented pattern of functional groups, generally termed molecular nanoparticles, with surgical precision. [18][19][20] Ab attery of single-isomer3 Dd isplays tailored towards nucleic acid complexation, targeting, and delivery has thus been produced, [21,22] examples record on covering cyclodextrin (CD), [23][24][25][26][27][28][29][30] calixarene, [31][32][33][34][35][36] macrocyclic peptides, [37][38][39][40] fullerene, [41][42][43][44] pillarene, [45][46][47] or cyclotrehalanp latforms. [48,49] These studies have focused on the influence of the molecular architecture of the vectoro nt he self-assembling and the nucleic acid delivery capabilities; however, none of them has pursued shape control of the vector-nucleic acid nanoparticles for the systematic study of its role fort he transfection efficiency.…”
Engineering self-assembled superstructures through complexation of plasmid DNA (pDNA) and single-isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self-assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)-based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod-type, or worm-like nanoparticles, which makes it possible to gain understanding of their shape-dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross-linking interactions on going from primary-face- to secondary-face-linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue-selective DNA delivery to the spleen in vivo.
“…For better biomedical applications, one of the strategies is to create the maintainable local reservoir of ROS scavenging agent with a single administration, [ 180–182 ] in which injectable hydrogels can be applied as carriers to deliver agents with controlled sizes to the targeted sites. ROS scavengers, covalently combined with the hydrogel skeletons by physically mixing or loading into particulate carriers, can be carried to the desired site by hydrogel injection.…”
Section: Engineering Biocatalytic and Antioxidant Nanostructures: Rational Design And Catalytic Activitiesmentioning
In human systems, reactive oxygen species (ROS) significantly affect different physiological activities and play critical roles in diverse living processes. It is widely known that excessive ROS generation in inflammatory tissues can further deteriorate the localized tissue injury and cause chronic diseases. Though promising for reducing ROS levels, many antioxidant molecules and natural enzymes suffer from abundant intrinsic limitations. Recently, a series of biocatalytic or antioxidant nanostructures have been designed with distinctive ROS scavenging capabilities, which show promising activities to overcome these kernel challenges. In this timely review, the most recent advances in engineering biocatalytic and antioxidant nanostructures for ROS scavenging are summarized. First, the ROS scavenging principles and corresponding methods for testing various enzymatic activities are carefully concluded. Subsequently, the rationally designed nanostructures with high ROS scavenging efficiencies are comprehensively discussed, especially on the catalytic activities, mechanisms, and structure‐function relationships. After that, the representative applications of these ROS scavenging nanostructures for diverse biotherapeutics are summarized in detail. At last, the primary challenges and future perspectives in this emerging research frontier have also been outlined. It is believed that this progress review will offer a cutting‐edge understanding and guidance to engineering future high‐performance ROS scavenging nanostructures for broad biotherapeutic applications.
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