Jianlin Long

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Abstract Gene therapy provides a novel method for cancer therapy. This study shows a DNA nanocomplex that is inspired from vesicular stomatitis virus (VSV) for ovarian cancer therapy. This DNA nanocomplex consists of a cationized monomethoxy poly (ethylene glycol)‐poly (d,l‐lactide) (MPEG‐PLA) nanoparticle and a plasmid encoding the matrix protein of vesicular stomatitis virus (VSVMP) that plays a critical role in the VSV‐induced apoptosis of cancer cells. The cationized MPEG‐PLA nanoparticle that is self‐assembled by MPEG‐PLA copolymer and N ‐[1‐(2,3‐dioleoyloxy) propyl]‐ N,N,N ‐trimethylammonium chloride (DOTAP) has low cytotoxicity and high transfection efficiency (&gt;80%). Intraperitoneal administration of the p VSVMP nanocomplex remarkably inhibits the intraperitoneal metastasis of ovarian cancer and does not cause significant systemic toxicity. The apoptosis induction and anti‐angiogenesis are involved in the anticancer mechanism. This work demonstrates a VSV‐inspired DNA nanocomplex that has potential application for the treatment of intraperitoneal metastasis of ovarian cancer.

INTRODUCTION: Circular RNAs (circRNAs) are deregulated in many types of human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functional role of circMYLK in NSCLC. MATERIALS AND METHODS: The expression levels of circMYLK and miR-195-5p in NSCLC tissues and cell lines were detected by RT-qPCR analysis. MTT assay, colony formation assay and transwell assay were performed to investigate the effects of circMYLK and miR-195-5p on the malignant phenotypes of NSCLC cells. The glucose consumption and lactate production of NSCLC cells were detected using commercial kits. The direct binding relation between circMYLK and miR-195-5p in NSCLC was predicted by bioinformatics analysis and validated by dual-luciferase reporter assay. RESULTS: The results showed that circMYLK was significantly up-regulated in NSCLC tissues and cell lines, and its high expression was closely associated with deleterious clinicopathological characteristics and poor prognosis of NSCLC patients. Knockdown of circMYLK remarkably inhibited the malignant phenotypes of NSCLC cells, including proliferation, migration, invasion, glucose consumption and lactate production. Moreover, circMYLK was identified as a molecule sponge for miR-195-5p, and glucose transporter member 3 (GLUT3) was shown to be a target gene of miR-195-5p in NSCLC. Further rescue experiments revealed that the oncogenic effects of circMYLK on NSCLC cells could be largely abrogated by co-transfection with miR-195-5p mimic. CONCLUSION: In summary, our study provides convincing evidence that circMYLK serves as a tumor promoter in NSCLC and can be used as a potential therapeutic target for NSCLC patients.

Currently, in vitro cancer cell culture technology is very important for cancer research. Existing studies have shown that two-dimensional (2D) cell environment may cause significant differences from tumor cells in vivo, resulting in high failure rates when the therapies developed in 2D tumor models translated to the clinic. And compared with 2D culture, the isotropic three-dimensional (3D) culture can construct an environment more similar to that in the body. Here, we utilized 3D printed porous microgel to culture for lung cancer cell and also explored possible mechanism of how 3D culture environment regulates actin cytoskeleton. Compared with 2D cultured lung cancer cells, cells in porous microgel are more similar to those extracted from the existing gold standard: mouse transplanted tumors, in terms of the ROCK-actin pathway. In addition, this study also revealed that ROCK pathway altered by environment played an important role in regulating the drug sensitivity of lung cancer cells. Hence, this 3D printed porous microgel is a promising lung cancer cell culture method, which shows potentional application in future cancer research and drug development.

Nanoparticles have great promise for gene delivery. However, the transfection efficiency of nanoparticle-based gene delivery systems is always unsatisfied to meet the requirement of effective gene therapy. Herein, we used low-dosage paclitaxel to enhance a nanoscaled gene delivery system that was self-assembled from N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammoniummethyl sulfate and monomethoxy poly(ethylene glycol)-poly(d,l-lactide) (DPP), creating a paclitaxel-encapsulated DPP (P-DPP) nanoparticle. The encapsulated low-dosage paclitaxel significantly improved the gene delivery efficiency of the DPP nanoparticles against multiple cancer cells, in some of which the transfection efficiency is as high as 92%. By the P-DPP nanoparticle, vesicular stomatitis virus matrix protein (VSVMP) that could induce cell apoptosis was delivered to treat ovarian cancer. The encapsulation of paclitaxel in DPP nanoparticles increased the expression of VSVMP, enhancing VSVMP to induce antiproliferation and apoptosis in SKOV3 ovarian cancer cells. Intraperitoneal administration of P-DPP-delivered VSVMP effectively inhibited the intraperitoneal metastasis of SKOV3 ovarian cancer, which was more efficient than DPP-delivered VSVMP. Moreover, it was found that the tumor cell apoptosis induction, tumor cell proliferation inhibition, and tumor angiogenesis suppression were involved in the anticancer mechanism of this nanocomplex. Our data suggest that the encapsulation of low-dosage paclitaxel can enhance the gene delivery efficiency of the DPP nanoparticles against multiple cancer cells and exert a synergistic anticancer effect with VSVMP gene in ovarian cancer treatment. The VSVMP gene therapy delivered by the paclitaxel-enhanced nanoparticle has potential application in ovarian cancer therapy.