The biological function of miR-128-2 in hepatocellular carcinoma and its molecular mechanism functioning.

BACKGROUND: Hepatocellular carcinoma (HCC) represents the major type of primary liver cancers, which is a most prevalent malignancy, as well as seriously threatens people's life and health. MiR-128-2 was reported to be associated with several human cancers, and is participated in the pathogenesis and development of cancers. Our research was performed to explore the expression profile and diagnostic significance of miR-128-2 in HCC. METHODS: The serum miR-128-2 expression was measured in 130 HCC subjects and 118 healthy people using quantitative real-time polymerase chain reaction (qRT-PCR) assay. Chi-square (ÿ2) test was utilized to estimate the relationship of miR-128-2 level with clinicopathological characteristic. In addition, the diagnostic accuracy of miR-128-2 in HCC was estimated via receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with healthy individuals, the level of miR-128-2 was obviously up-regulated in HCC cases (P < 0.01). And its level was closely related to AFP level (P = 0.013), TNM stage (P = 0.009) and differentiation (P = 0.036). Nevertheless, there was no obvious relationship with age, gender, tumor size, HBV status, ALT or metastasis (all P > 0.05). According to the ROC curve, serum miR-128-2 had a high value in discriminating HCC cases from control individuals, with a AUC value of 0.880 combing with the sensitivity of 79.2% and the specificity of 83.9%. CONCLUSION: The serum level of miR-128-2 in cases with HCC was obviously increased, which was related to the malignant progression of HCC. Due to the reasonable sensitivity and specificity, miR-128-2 might be as a new and effective marker for the diagnosis of HCC.

Biomimetic and temporal-controlled nanocarriers with ileum transporter targeting for achieving oral administration of chemotherapeutic drugs.

BACKGROUND: Oral chemotherapy is preferred for patients with cancer owing to its multiple advantages, including convenience, better patient compliance, and improved safety. Nevertheless, various physical barriers exist in this route that hamper the development of oral chemotherapeutic formulations, including destruction of drugs in the gastrointestinal tract (GIT), low permeability in enterocytes, and short residence time in the intestine. To overcome these limitations, it is necessary to design an efficient oral drug delivery system with high efficacy and improved safety. RESULTS: Herein, we designed novel glycocholic acid (GCA)-functionalized double layer nanoparticles (GCA-NPs), which can act via an endogenous pathway and in a temporally controlled manner in the intestine, to enhance the oral bioavailability of hydrophobic chemotherapeutic drugs such as paclitaxel (PTX). GCA-NPs were composed of quercetin (Qu)-modified liposomes (QL) coated with GCA-chitosan oligosaccharide conjugate (GCOS). The GCA-NPs thus prepared showed prolonged intestinal retention time and good GIT stability due to the presence of chitosan oligosaccharide (COS) and enhanced active transportation via intestinal apical sodium-dependent bile acid transporter (ASBT) due to the presence of GCA. GCA-NPs also efficiently inhibited intestinal P-gp induced by Qu. PTX-loaded GCA-NPs (PTX@GCA-NPs) had a particle size of 84 nm and an entrapment efficiency of 98% with good stability. As a result, the oral bioavailability of PTX was increased 19-fold compared to that of oral Taxol® at the same dose. Oral PTX@GCA-NPs displayed superior antitumor efficacy and better safety than Taxol® when administered intravenously. CONCLUSIONS: Our novel drug delivery system showed remarkable efficacy in overcoming multiple limitations and is a promising carrier for oral delivery of multiple drugs, which addresses several challenges in oral delivery in the clinical context.

Targeted therapeutic effects of oral inulin-modified double-layered nanoparticles containing chemotherapeutics on orthotopic colon cancer.

Colon cancer is emerging as one of the most prevalent cancers globally. Oral colonic drug delivery systems have attracted considerable attention in the treatment of orthotopic colon cancer due to their superior properties. However, the particularity and complexity of the gastrointestinal structure are a hindrance to the safe delivery of drugs to the target site of the colon tumor. Herein, to achieve an effective delivery system specifically targeting the colon, we designed paclitaxel (PTX)-loaded oral colon double-targeted nanoparticles using polylactic acid-polyethyleneimine (PLA-PEI) and hyaluronic acid-inulin (HA-IN). IN is enzyme sensitive and hardly degraded in the upper digestive tract; as such, it can ensure the safe delivery of nanoparticles to the colon. The "IN shell" is degraded by colon-specific bacteria at the colon site. The exposed HA not only promotes intestinal mucosal crossing of nanoparticles, but also acts as the target of CD44 and plays an active targeting role in tumor tissues. The action of the proton sponge effect of PEI induces the successful release of the nanoparticle. The prepared nanoparticles have a negative charge of -19.5 ± 1.2 mV and a size of 176.7 ± 0.3 nm with a narrow PDI of 0.148 ± 0.004. C26 cells were used for in vitro anticancer studies, including fluorescence staining and flow cytometry, and to explore inhibition of proliferation. The analysis demonstrated that the nanoparticles were more efficiently taken up by cancer cells, exhibiting greater cytotoxicity and apoptosis-inducing ability compared to free drugs. Moreover, in vivo studies revealed that the nanoparticles could remain in vivo for 24 h and accumulate at the tumor site. These data provide evidence of the therapeutic effect on orthotopic colon cancer. Also, safety evaluation results demonstrated that PLA-PEI/HA-IN is a safe drug delivery vector, therefore, holds great promise as a new therapeutic strategy for orthotopic colon cancer treatment.