Preparation and anti-tumor effects of mesoporous silica nanoparticles loaded with trifluoperazine.

We have developed a targeted nano-drug delivery system that effectively harnesses the anti-tumor properties of trifluoperazine (TFP), while concurrently mitigating its side effects on the central nervous system. The manufacturing process entailed the preparation of mesoporous silica nanoparticles (MSN-NH2), followed by the loading of trifluoperazine into the pores of MSN-NH2 and then surface modification with polyethylene glycol (PEG) and anisamide (AA), resulting in the formation of TFP@MSN@PEG-AA (abbreviated as TMPA) nanoparticles. In vitro and in vivo anti-tumor activity and hemolysis experiments showed that TMPA had an excellent safety profile and a good anti-tumor effect. Importantly, the drug content of the TMPA nanoparticle group was found to be significantly lower than that of the TFP group in the mouse brain tissue as determined by High Performance Liquid Chromatography (HPLC) detection. Therefore, the developed drug delivery system achieved the goal of maintaining TFP's anti-tumor action while avoiding its negative effects on the central nervous system.

Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features.

Clear cell renal cell carcinoma (ccRCC) is a major pathological type of kidney cancer with a poor prognosis due to a lack of biomarkers for early diagnosis and prognosis prediction of ccRCC. In this study, we investigated the aberrant expression of Acyl-coenzyme A oxidase 1 (ACOX1) in ccRCC and evaluated its potential in diagnosis and prognosis. ACOX1 is the first rate-limiting enzyme in the peroxidation ß-oxidation pathway and is involved in the regulation of fatty acid oxidative catabolism. The mRNA and protein levels of ACOX1 were significantly downregulated in ccRCC, and its downregulation was closely associated with the tumor-node-metastasis stage of patients. The ROC curves showed that ACOX1 possesses a high diagnostic value for ccRCC. The OS analysis suggested that lower expression of ACOX1 was closely related to the worse outcome of patients. In addition, gene set enrichment analysis suggested that expression of ACOX1 was positively correlated with CDH1, CDH2, CDKL2, and EPCAM, while negatively correlated with MMP9 and VIM, which strongly indicated that ACOX1 may inhibit the invasion and migration of ccRCC by reversing epithelial-mesenchymal transition. Furthermore, we screened out that miR-16-5p is upregulated at the mRNA transcript level in ccRCC and negatively correlated with ACOX1. In conclusion, our results showed that ACOX1 is abnormally low expressed in ccRCC, suggesting that it could serve as a diagnostic and prognostic biomarker for ccRCC. Overexpression of miR-16-5p may be responsible for the inactivation of ACOX1.

Preparation of multifunctional mesoporous SiO2nanoparticles and anti-tumor action.

A targeted drug delivery system was developed to accumulate specific drugs around tumor cells based on the redox, temperature, and enzyme synergistic responses of mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-NH2) and Doxorubicin (DOX) for tumor therapy were prepared and loaded into the pores of MSN- NH2 to obtain DOX@MSN(DM NPs). Hyaluronic acid (HA) was used as the backbone and disulfide bond was used as the linker arm to graft carboxylated poly (N-isopropylacrylamide)(PNIPAAm-COOH) to synthesize the macromolecular copolymer (HA-SS-PNIPAAm), which was modified to DM NPs with capped ends to obtain the nano-delivery system DOX@MSN@HA-SS-PNIPAAm(DMHSP NPs), and a control formulation was prepared in a similar way. DMHSP NPs specifically entered tumor cells via CD44 receptor-mediated endocytosis; the high GSH concentration (10 mM) of cells severed the disulfide bonds, the hyaluronidase sheared the capped HA to open the pores, and increased tumor microenvironment temperature due to immune response can trigger the release of encapsulated drugs in thermosensitive materials.In vitroandin vivoantitumor and hemolysis assays showed that DMHSP NPs can accurately target hepatocellular carcinoma cells with a good safety profile and have synergistic effects, which meant DMHSP NPs had great potential for tumor therapy.

A pH-responsive mesoporous silica nanoparticle-based drug delivery system for targeted breast cancer therapy.

In order to make the drug specifically aggregate at the tumor site, we had developed a targeted drug delivery system based on pH responsive mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-COOH) were prepared and doxorubicin (DOX) was loaded into the pores of MSN-COOH, and then polyethyleneimine (PEI) and anisamide (AA) were modified on the surface of mesoporous silica, named DOX@MSN-PEI-AA(DMPA). DMPA specifically entered tumor cells through AA-mediated receptor endocytosis; PEI dissociated from the surface of the MSN in the acidic environment of cellular lysosomes/endosomes due to protonation of PEI, resulting in steady release of the encapsulated DOX from the pores of MSN in the cytoplasm of the target cells. In vitro and in vivo anti-tumor experiments and hemolytic experiments indicated that DMPA can accurately target breast cancer cells and show excellent safety at the same time, showing great potential for tumor therapy.