Delivery of miR-375 and doxorubicin hydrochloride by lipid bilayer coated hollow mesoporous silica nanoparticles for liver cancer therapy / 药学学报

This study was designed to prepare a novel lipid bilayer coated hollow mesoporous silica nanocarrier for co-delivery of gene drugs and chemotherapeutic drugs to enhance the inhibitory activity of antitumor drugs in hepatoma cells. Hollow mesoporous silica was synthesized by modified StÖber method. Lipid-fusion principle was used to prepare lipid-hollow co-loaded doxorubicin (DOX) and miR-375 (LHMSN-DOX/miR-375). Meanwhile, the morphology, particle size, surface potential, drug loading and release were characterized in vitro. The inhibition of cell proliferation, cell migration and invasion was then evaluated. The results indicated that the core-shell structure of LHMSN-DOX/miR-375 was clear with an intact outer lipid membrane and an ordered internal HMSN mesoporous structure. The drug release amount was pH responsive while the drug was rapidly released under simulated intracellular acidic conditions relative to normal physiological environment. Compared with free DOX, LHMSN-DOX/miR-375 can deliver DOX and miR-375 to liver cancer cells and inhibit the proliferation, migration and invasion of cells more effectively.

Anticancer Opportunity Created by Loss of Tumor Suppressor Genes.

Deletion of oncosuppressors occurs frequently in the cancer genome. A great deal of effort has been made to therapeutically restore the lost function of oncosuppressors, with little clinically translatable success, however. Reassuringly, besides the disappointing restoration endeavors, oncosuppressor loss can be therapeutically exploited in several other ways, such as the "synthetic lethality" strategies and the "therapeutic vulnerability" created by codeletion of neighboring genes. The study by Liu et al showed that codeletion of p53 and a neighboring essential gene POLR2A rendered colon cancer cells highly sensitive to further inhibition of POLR2A both in vitro and in vivo In recent years, several studies have reported similar phenomenon in a wide range of cancer types. In this focus article, we will introduce several kinds of anticancer opportunities created by the loss of oncosuppressors and discuss their mechanisms. Given the frequency of oncosuppressor loss in cancer, its therapeutic exploitation rather merits further investigation and may open a new window for oncotherapy.

LINE-1 in cancer: multifaceted functions and potential clinical implications.

Long interspersed nuclear element-1 (L1) retrotransposons are jumping genes that comprise 17% of human DNA. They utilize a ''copy-and-paste'' mechanism to propagate themselves throughout the genome via RNA intermediates, a process termed retrotransposition. L1s are active in the germ line and during embryogenesis, yet they are epigenetically suppressed in somatic cells. In cancer cells, however, L1s are aberrantly activated and may have a role in genome instability, one of the hallmarks of cancer pathogenesis. Their methylation states and retrotransposition activities are associated with and fluctuate during cancer initiation and progression, thus representing promising diagnostic biomarkers and therapeutic targets. During tumorigenesis, L1s exert both retrotransposition-dependent and retrotransposition-independent functions. The former may result in alterations in target gene expression or chromosomal rearrangement, or drive Alu and SVA, events that could function in tumorigenesis, whereas the latter can potentially exert epigenetic regulation by generating endo-siRNAs, forming chimeric L1 transcripts or changing the expression of adjacent genes by providing novel splicing sites or alternative promoters. Moreover, the L1 encoded proteins, ORF1p and ORF2p, may have pro-oncogenic potential by, for example, activating oncogenic transcriptional factors or sequestering oncosuppressors. Herein, we introduce the components and mechanisms of L1 retrotransposition, discuss the landscape, possible functions, and regulation of L1 activity in cancer, and seek their potential as diagnostic biomarkers and therapeutic targets.Genet Med 18 5, 431-439.

CRISPR-Cas9: a new and promising player in gene therapy.

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a cost-effective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9-mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy.

[Study of nitrogen silicon zirconium-hydroxylapatite as a coating on pure titanium implantation].

OBJECTIVE: To compare the osseointegration and corrosion of different kind of coatings on pure titanium. METHODS: By plasma spraying technology, nitrogen silicon zirconium-hydroxylapatite (ZrSiN-HA) compound coating was prepared on the surface of pure titanium and the pure titanium was implanted with the mandible of the experimental animal. The superficial appearance of the compound coating was observed and analyzed by scanning electron microscope (SEM). The ZrSiN-HA, nitrogen silicon zirconium (ZrSiN), hydroxylapatite (HA) and pure titanium were compared and examined. In the four groups, the bone binding force of coatings were detected, and the superficial appearance of the break regions were observed by the electronic multipurpose material testing aircraft. In the four groups, the anticorrosive of coatings were compared and examined on the electrochemistry corrosion testing system. RESULTS: Experimental results indicated that the implant surface sprayed with the ZrSiN-HA was more compact than that sprayed with HA. The crystallization was obvious. Compared with the other coatings, the bone binding force of the ZrSiN-HA coating was the highest, and its anticorrosive performance was the strongest. CONCLUSION: The application of ZrSiN-HA coating is advantageous to the long-term retention of implant, and it has huge latent application value to dental dummy.