Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles.

Cancer remains a significant threat to human health. While numerous therapies have been developed to combat the disease, traditional treatments such as chemotherapy and radiotherapy are suboptimal and associated with significant side effects. Gene therapy is an emerging therapeutic approach that offers improved targeting and reduced side effects compared with traditional treatments. Using siRNA and other nucleic acid-based drugs in cancer treatment has generated significant interest among researchers. Nanocarriers, such as liposomes, can effectively deliver these agents to tumor sites. However, gene therapy alone is often insufficient to eradicate tumors, and there is a risk of recurrence. Therefore, combining gene therapy with other therapies using nanocarriers, such as phototherapy and magnetic hyperthermia therapy, can lead to synergistic therapeutic effects through different mechanisms. In this review, we summarize various ways in which gene therapy can be combined with other therapies and highlight the role of nanoplatforms in mediating these combined therapies, which would inspire novel design ideas toward combination therapies. Additionally, bottlenecks and barriers to gene therapy should be addressed in the near future to achieve better clinical efficacy.

Combinational application of metal-organic frameworks-based nanozyme and nucleic acid delivery in cancer therapy.

The rapid development of nanotechnology has generated numerous ideas for cancer treatment, and a wide variety of relevant nanoparticle platforms have been reported. Metal-organic frameworks (MOFs) have been widely investigated as an anti-cancer drug delivery vehicle owing to their unique porous hybrid structure, biocompatibility, structural tunability, and multi-functionality. MOF materials with catalytic activity, known as nanozymes, have applications in photodynamic and chemodynamic therapy. Nucleic acids have also attracted increasing research attention owing to their programmability, ease of synthesis, and versatility. A variety of functional DNAs and RNAs have been applied both therapeutically (gene-targeting drugs for cancer treatment) and nontherapeutically (used as modified materials to enhance the therapeutic effects of other nanomedicines). The combined use of MOFs and functional nucleic acids have been extensively investigated and has been associated with excellent tumor-suppressor activity in various treatment methods. In this review, we summarize the progress in the research and development of tumor therapy based on MOFs and nucleic acid delivery over recent years, focusing on the combinational use of different delivery and design strategies for MOF/therapeutic nucleic acid platforms. We further summarize the strategies for combining MOFs (universal carrier, functional carrier) and nucleic acids (therapeutic nucleic acids, nontherapeutic nucleic acids) and discuss the corresponding therapeutic effects in cancer treatment. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

PM2.5 induces the distant metastasis of lung adenocarcinoma via promoting the stem cell properties of cancer cells.

Lung cancer is the most common cancer in China and second worldwide, of which the incidence of lung adenocarcinoma is rising. As an independent factor, air pollution has drawn the attention of the public. An increasing body of studies has focused on the effect of PM2.5 on lung adenocarcinoma; however, the mechanism remains unclear. We collected the PM2.5 in two megacities, Beijing (BPM) and Shijiazhuang (SPM), located in the capital of China, and compared the different components and sources of PM2.5 in the two cities. Vehicle emissions are the primary sources of BPM, whereas SPM is industrial emissions. We found that chronic exposure to PM2.5 promotes the tumorigenesis and metastasis of lung adenocarcinoma in patient-derived xenograft (PDX) models, as well as the migration and invasion of lung adenocarcinoma cell lines. SPM has more severe effects in vivo and in vitro. The underlying mechanisms are related to the stem cell properties of cancer cells, the epithelial-mesenchymal transition (EMT) process, and the corresponding miRNAs. It is hopeful to provide a theoretical basis for improving air pollution in China, especially in the capital area, and is of the significance of long-term survival of lung cancer patients.

Titanium dioxide nanoparticles perturb the blood-testis barrier via disruption of actin-based cell adhesive function.

As one of the most commonly used nanoparticles, titanium dioxide nanoparticles (TiO2-NPs) are widely used as coating reagents in cosmetics, medicine and other industries. The increasing risk of exposure to TiO2-NPs raises concerns about their safety. In this study, we investigated the mechanism by which TiO2-NPs cross the blood-testis barrier (BTB). TM-4 cells were selected as an in vitro Sertoli cell model of BTB. Cell viability, cell morphological changes, apoptosis, oxidative damage, and the expression levels of actin regulatory and tight junction (TJ) proteins were assessed in TM-4 cells treated with 3-nm and 24-nm TiO2-NPs. Cells treated with 3-nm TiO2-NPs exhibited increased cytotoxicity and decreased Annexin II expression, whereas cells treated with 24-nm TiO2-NPs exhibited increased Arp 3 and c-Src expression. Both TiO2-NPs induced significant oxidative stress, decreased the expression of TJ proteins (occludin, ZO-1 and claudin 5), damaged the TJ structure, and exhibited enlarged gaps between TM-4 cells. Our results indicated that both TiO2-NPs crossed the BTB by disrupting actin-based adhesive junctions of TM-4 cells; however, apoptosis was not observed. Our results provide new insights into how TiO2-NPs cross the BTB.

Enzyme-Triggered Disassembly of Perylene Monoimide-based Nanoclusters for Activatable and Deep Photodynamic Therapy.

Photodynamic therapy (PDT) exhibits great potential for cancer therapy, but still suffers from nonspecific photosensitivity and poor penetration of photosensitizer. Herein, a smart perylene monoimide-based nanocluster capable of enzyme-triggered disassembly is reported as an activatable and deeply penetrable photosensitizer. A novel carboxylesterase (CE)-responsive tetrachloroperylene monoimide (P1) was synthesized and assembled with folate-decorated albumins into a nanocluster (FHP) with a diameter of circa 100 nm. Once P1 is hydrolyzed by the tumor-specific CE, FHP disassembles into ultrasmall nanoparticles (ca. 10 nm), facilitating the deep tumor penetration of FHP. Furthermore, such enzyme-triggered disassembly of FHP leads to enhanced fluorescence intensity (ca. 8-fold) and elevated singlet oxygen generation ability (ca. 4-fold), enabling in situ near-infrared fluorescence imaging and promoted PDT. FHP permits remarkable tumor inhibition in vivo with minimal side effects through imaging-guided, activatable, and deep PDT. This work confirms that this cascaded multifunctional control through enzyme-triggered molecular disassembly is an effective strategy for precise cancer theranostics.