Complexes of Pro-Apoptotic siRNAs and Carbosilane Dendrimers: Formation and Effect on Cancer Cells

Krasheninina, Olga; Apartsin, Evgeny; Fuentes, Elena; Szulc, Agata; Йонов, Максим; Venyaminova, Alya G.; Shcharbin, Dzmitry; Mata, F. Javier de la; Bryszewska, Maria; Gómez, Rafael

doi:10.3390/pharmaceutics11010025

Cited by 25 publications

(28 citation statements)

References 44 publications

(64 reference statements)

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“…The stoichiometric ratios of complexes determined by gel electrophoresis were confirmed by measurement of changes in the zeta potential during titration of siRNA with AgNPs [ 37 , 38 ]. Further, this assay showed the positive surface electrostatic potential of complexes, which was also demonstrated for dendriplexes [ 39 , 40 , 41 ], including those formed by carbosilane dendrimers and siBcl-xl [ 22 , 42 ]. This feature is crucial for the intracellular delivery of the cargo, since positively charged nanosystems can penetrate cell membranes more effectively than neutral or negatively charged ones [ 43 ].…”

Section: Discussionmentioning

confidence: 64%

“…Despite intracellular delivery of siRNA by AgNPs (demonstrated by confocal microscopy), no increase in cytotoxic activity of AgNP:siRNA complexes was found compared to free nanoparticles. This may be due to several factors, including hampered endosomal escape after endocytosis, limited release of siRNA from complexes, or an inadequate amount of intracellularly delivered siRNA to exert its cytotoxic effect [42]. On the other hand, the expression of Bcl-xl and other proteins of Bcl-2 family in HeLa cells is relatively low ( [50,51], www.proteinatlas.org), which at the present stage makes it impossible to draw unequivocal conclusions about the effectiveness of the proposed siRNA delivery vehicles.…”

Section: Discussionmentioning

confidence: 99%

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Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA

Pedziwiatr-Werbicka

Gorzkiewicz

Horodecka

et al. 2020

IJMS

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Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl). Using gel electrophoresis, zeta potential and hydrodynamic diameter measurements, as well as transmission electron microscopy, we characterized AgNP:siRNA complexes and demonstrated the stability of nucleic acid in complexes in the presence of RNase. Hemolytic properties of free silver nanoparticles and complexes, their effect on lymphocyte proliferation and cytotoxic activity on HeLa cells were also examined. Confocal microscopy proved the effective cellular uptake of complexes, indicating the possible use of this type of silver nanoparticles as carriers of genetic material in gene therapy.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA

Pedziwiatr-Werbicka

Gorzkiewicz

Horodecka

et al. 2020

IJMS

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“…Dendritic molecules, dendrimers and dendrons, are versatile platforms to design supramolecular nanoconstructions for robust drug delivery [ 4 , 5 , 6 , 7 , 8 ]. In particular, carbosilane dendrimers are efficient tools for antibacterial [ 9 ] and antiviral therapy [ 10 ], nucleic acid delivery [ 11 ], cancer treatment [ 12 ], imaging [ 13 ], functional nanomaterials [ 14 , 15 ], and so on. It should be noted that dendritic architectures give room to design various types of supramolecular constructions based on the molecular topology of building blocks.…”

Section: Introductionmentioning

confidence: 99%

pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

et al. 2020

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Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species—triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.

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“…In the recent years, several lipid molecules [7][8][9], cationic polymers [10,11], inorganic nanoparticles and other systems have been investigated for nucleic acid delivery [12][13][14]. Cationic materials are able to form nano-sized complexes through electrostatic interactions and efficiently protect their payload.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

et al. 2020

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The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.

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Complexes of Pro-Apoptotic siRNAs and Carbosilane Dendrimers: Formation and Effect on Cancer Cells

Cited by 25 publications

References 44 publications

Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA

Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA

pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

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