Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma

Xia, Yu; Tang, Guo‐Yi; Chen, Yi; Wang, Changbing; Guo, Min; Xu, Tiantian; Zhao, Mingqi; Zhou, Yongjian

doi:10.1016/j.bioactmat.2020.10.019

Cited by 45 publications

(31 citation statements)

References 50 publications

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“…Therefore, discovering an effective and safe vehicle as a gene therapy tool would be helpful for the treatment of SCI. Plasmids are accessible tools for modulating molecule expression, delivering plasmids using biological materials could enhance plasmid efficiency, concentration and biological stability [ 16 ]. In particular, liposome-based nanoparticles are known to be good carriers for the loading, transport and release of plasmids to their target [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Zhang

Xiong

et al. 2021

Bioactive Materials

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Oxidation resistance 1 (OXR1) is regarded as a critical regulator of cellular homeostasis in response to oxidative stress. However, the role of OXR1 in the neuronal response to spinal cord injury (SCI) remains undefined. On the other hand, gene therapy for SCI has shown limited success to date due in part to the poor utility of conventional gene vectors. In this study, we evaluated the function of OXR1 in SCI and developed an available carrier for delivering the OXR1 plasmid (pOXR1). We found that OXR1 expression is remarkably increased after SCI and that this regulation is protective after SCI. Meanwhile, we assembled cationic nanoparticles with vitamin E succinate-grafted ε-polylysine (VES-g-PLL) (Nps). The pOXR1 was precompressed with Nps and then encapsulated into cationic liposomes. The particle size of pOXR1 was compressed to 58 nm, which suggests that pOXR1 can be encapsulated inside liposomes with high encapsulation efficiency and stability to enhance the transfection efficiency. The agarose gel results indicated that Nps-pOXR1-Lip eliminated the degradation of DNA by DNase I and maintained its activity, and the cytotoxicity results indicated that pOXR1 was successfully transported into cells and exhibited lower cytotoxicity. Finally, Nps-pOXR1-Lip promoted functional recovery by alleviating neuronal apoptosis, attenuating oxidative stress and inhibiting inflammation. Therefore, our study provides considerable evidence that OXR1 is a beneficial factor in resistance to SCI and that Nps-Lip-pOXR1 exerts therapeutic effects in acute traumatic SCI.

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Section: Introductionmentioning

confidence: 99%

Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Zhang

Xiong

et al. 2021

Bioactive Materials

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“…It is well known that the main mechanism for the entry of nanodrugs and therapeutic genes into the cell is endocytosis which determines the targeted delivery of nanoparticles [ 27 ]. Moreover, there are several types of endocytosis: micropinocytosis, caveolar, and clathrin-associated endocytosis.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of Ca2+-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels

Turovsky

Varlamova

2021

Biology

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To date, there are practically no data on the mechanisms of the selenium nanoparticles action on calcium homeostasis, intracellular signaling in cancer cells, and on the relationship of signaling pathways activated by an increase in Ca2+ in the cytosol with the induction of apoptosis, which is of great importance. The study of these mechanisms is important for understanding the cytotoxic effect of selenium nanoparticles and the role of this microelement in the regulation of carcinogenesis. The work is devoted to the study of the role of selenium nanoparticles obtained by laser ablation in the activation of the calcium signaling system and the induction of apoptosis in human glioblastoma cells (A-172 cell line). In this work, it was shown for the first time that the generation of Ca2+ signals in A-172 cells occurs in response to the application of various concentrations of selenium nanoparticles. The intracellular mechanism responsible for the generation of these Ca2+ signals has also been established. It was found that nanoparticles promote the mobilization of Ca2+ ions from the endoplasmic reticulum through the IP3-receptor. This leads to the activation of vesicular release of ATP through connexin hemichannels (Cx43) and paracrine cell activation through purinergic receptors (mainly P2Y). In addition, it was shown that the activation of this signaling pathway is accompanied by an increase in the expression of pro-apoptotic genes and the induction of apoptosis. For the first time, the role of Cx43 in the regulation of apoptosis caused by selenium nanoparticles in glioblastoma cells has been shown. It was found that inhibition of Cx43 leads to a significant suppression of the induction of apoptosis in these cells after 24 h treatment of cells with selenium nanoparticles at a concentration of 5 µg/mL.

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“…In a recent study, a positively charged peptide was installed on the surface of selenium to forge a tumor‐targeted siRNA delivery carrier. [ 120 ] Selenium was synthesized from a solution of Na 2 SeO 3 and vitamin C. The modified 80 nm selenium nanoparticles obtained were able to form a stable suspension, significantly bind siRNA, and protect it from degradation. [ 121 ] In cases of bone‐related delivery of drugs and genes, calcium phosphate can be considered a good candidate for in vitro and in vivo transfection.…”

Section: Nanocarriersmentioning

confidence: 99%

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

et al. 2021

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In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA‐based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology‐assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in‐depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology‐mediated RNA therapies are discussed.

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Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma

Cited by 45 publications

References 50 publications

Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Mechanism of Ca2+-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

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