Research Progress on the Anti-Cancer Molecular Mechanisms of Huaier.

Huaier (Trametes robiniophila Murr), a Chinese traditional herb of medicine, has demonstrated promising curative effects in clinical treatment for various tumors. There are documented experiments showing the biological functions of Huaier with its antineoplastic molecular mechanisms: restraining proliferation and metastasis, arresting cell cycle, inducing apoptosis, pyrosis, and autophagy, anti-intratumoral angiogenesis, attenuating characteristics of tumor stem-like cells, interfering with the function of the tumor-related immune system, reversing drug resistance, and enhancing the sensitivity to chemotherapeutic drugs, etc. In addition, studies suggest that non-coding RNA (ncRNA) acts a pivotal part in cancer occurrence and development, and demonstrates that Huaier adjusts the performance of certain lncRNA (long non-coding RNA) and proceeds to affect the microRNA and its target genes, rendering an anti-tumor effect. Huaier also modulates the expression of lncRNA to attenuate the activity of ncRNA-sponged microRNA and then inhibits the expression of downstream target genes. We summarize and illustrate the experimentally confirmed anti-cancer molecular mechanisms of Huaier, to inspire new ideas for researchers in relevant fields.

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting.

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures. In this review, we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations, aiming at providing guidance in the overall design of precise nanomedicine. Additionally, future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.

The role of antibody delivery formation in cancer therapy.

Cancer has become one of the major threats to human survival. Because of antibodies specificity and low toxicity, it is the primary choice to diagnose and treat cancer. It is easy to be cleared from the blood circulation or distributing throughout the body and causes unnecessary side effects. It is necessary to delivery antibodies to the tumour region in a stable, safe and effective manner. In this review, we discuss the latest studies that aimed to delivery antibodies to tumour sites via several vector forms, such as liposomes, carbon nanomaterials, and gold nanomaterials. How to deliver antibodies to the target site is a difficulty for antibody therapy. This review summarises the antibody's therapeutic forms and carrier materials in recent years, and to explore how antibodies can be safely and stably delivered to the target site.

ROS/p53/miR­335­5p/Sp1 axis modulates the migration and epithelial to mesenchymal transition of JEG­3 cells.

Differential expression of microRNA (miR)­335­5p, a key tumor suppressor, has been detected in pre­eclampsia (PE) placentas. However, the role of miR­335­5p in the pathogenesis of PE and the factor modulating its aberrant expression remain unknown. The present study used JEG­3 cells in vitro to investigate these mechanisms. The role of miR­335­5p in proliferation, apoptosis and migration of JEG­3 cells was investigated using MTT, Annexin V­FITC/PI, Transwell migration and wound healing assays, respectively. miR­335­5p expression levels were analyzed using reverse transcription­quantitative PCR. The expression levels of E­cadherin, N­cadherin, Snail, specificity protein 1 (Sp1) and p53 were assessed using western blot analysis. Cell viability analysis was performed using the Cell Counting Kit­8 assay. The intracellular reactive oxygen species (ROS) levels were detected using a 2,7­dichlorodihydrofluorescein diacetate assay. The present results suggested that miR­335­5p did not affect the proliferation or apoptotic rate of JEG­3 cells. Overexpression of miR­335­5p significantly inhibited the migration of JEG­3 cells, decreased the expression levels of Sp1, N­cadherin and Snail, and increased E­cadherin expression. Sp1 silencing produced similar results in JEG­3 cells. H2O2 significantly increased the intracellular ROS levels and miR­335­5p expression, whereas N­acetyl­cysteine pretreatment prior to H2O2 treatment reversed the increases in miR­335­5p expression. Knockdown of p53 significantly decreased the expression levels of miR­335­5p in JEG­3 cells and in H2O2­treated cells. The present results suggested that miR­335­5p expression levels in trophoblast cells could be increased by ROS in a p53­dependent manner, leading to the downregulation of Sp1 and subsequent inhibition of epithelial to mesenchymal transition and cell migration. The present results may provide novel evidence on the etiology of PE.

Ethosomal Gel for Improving Transdermal Delivery of Thymosin ß-4.

PURPOSE: Thymosin ß-4(Tß-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tß-4 as a model drug wrapped into ethosomes. METHODS: We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model. RESULTS: Optimized Tß-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-ß4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-ß4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time. CONCLUSION: Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.

Enzyme responsiveness enhances the specificity and effectiveness of nanoparticles for the treatment of B16F10 melanoma.

The clinical treatment of melanoma continues to present many challenges including poor prognosis because neither monotherapy nor combination therapies have shown maximal treatment efficacy. In this study, an enzyme-responsive nanoparticle was designed for tumor subtypes with the high expression of heparanase-1, since highly metastatic tumors such as melanoma generally express significant levels of heparanase-1. PTX-DOTAP@alloferon-1-heparin/protamine, an enzyme-responsive nanoparticle, has a particle size of 106.1 ± 1.113 nm and a ζ-potential of -45.1 ± 0.455 mV, which enables enrichment in the tumor site by passive targeting. Subsequently, heparanase-1, which is highly expressed in the extracellular matrix, rapidly recognizes and degrades heparin in the outer layer of the nanoparticle and releases encapsulated alloferon-1 by ion diffusion to activate inhibited NK cells in the tumor microenvironment. The size of the smart nanoparticle will eventually decrease to 59.30 ± 0.783 nm and the ζ-potential will reverse to 25.4 ± 0.257 mV, which is beneficial for deep penetration and tumor cell uptake (due to the high negative charge on the tumor cell surface) of PTX-DOTAP cores. Paclitaxel is released in the cytoplasm, and the tumor cells are arrested in the G2/M phase. The nanoparticle characterization experiment demonstrated that in vivo drug delivery could be completed. In subsequent cell and animal experiments, the experimental data demonstrated the efficient therapeutic effects of the nanoparticle. This study provides an excellent template nanoparticle for the treatment of highly metastatic tumors to enhance future prognosis.