Boosting chemotherapy of bladder cancer cells by ferroptosis using intelligent magnetic targeting nanoparticles.

A versatile nano-delivery platform was reported to enhance the tumor suppression effect of chemotherapy by augmenting tumor cells' ferroptosis. The platform consists of pomegranate-like magnetic nanoparticles (rPAE@SPIONs) fabricated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within a reduced poly(ß-amino ester)s-PEG amphiphilic copolymer (rPAE). The resulting platform exhibits several functionalities. Firstly, it promotes the doxorubicin (DOX) release by leveraging the mild hyperthermia generated by NIR irradiation. Secondly, it triggers ferroptosis in tumor cells, inducing their demise. Thirdly, it induces polarization of macrophages towards an anti-tumor M1 phenotype, contributing to ferroptosis of tumor cells and enhanced tumor cell suppression. This study effectively capitalizes on the versatility of SPIONs and offers a simple yet powerful strategy for developing a new nanosized ferroptosis-inducing agent, ultimately improving the inhibition of bladder cancer cells.

Cationic Polymers as Transfection Reagents for Nucleic Acid Delivery.

Nucleic acid therapy can achieve lasting and even curative effects through gene augmentation, gene suppression, and genome editing. However, it is difficult for naked nucleic acid molecules to enter cells. As a result, the key to nucleic acid therapy is the introduction of nucleic acid molecules into cells. Cationic polymers are non-viral nucleic acid delivery systems with positively charged groups on their molecules that concentrate nucleic acid molecules to form nanoparticles, which help nucleic acids cross barriers to express proteins in cells or inhibit target gene expression. Cationic polymers are easy to synthesize, modify, and structurally control, making them a promising class of nucleic acid delivery systems. In this manuscript, we describe several representative cationic polymers, especially biodegradable cationic polymers, and provide an outlook on cationic polymers as nucleic acid delivery vehicles.

Poly(ß-amino ester)s-based nanovehicles: Structural regulation and gene delivery.

The first poly(ß-amino) esters (PßAEs) were synthesized more than 40 years ago. Since 2000, PßAEs have been found to have excellent biocompatibility and the capability of ferrying gene molecules. Moreover, the synthesis process of PßAEs is simple, the monomers are readily available, and the polymer structure can be tailored to meet different gene delivery needs by adjusting the monomer type, monomer ratio, reaction time, etc. Therefore, PßAEs are a promising class of non-viral gene vector materials. This review paper presents a comprehensive overview of the synthesis and correlated properties of PßAEs and summarizes the progress of each type of PßAE for gene delivery. The review focuses in particular on the rational design of PßAE structures, thoroughly discusses the correlations between intrinsic structure and effect, and then finishes with the applications and perspectives of PßAEs.

The nanoformula of zoledronic acid and calcium carbonate targets osteoclasts and reverses osteoporosis.

Osteoporosis is known as an imbalance in bone catabolism and anabolism. Overactive bone resorption causes bone mass loss and increased incidence of fragility fractures. Antiresorptive drugs are widely used for osteoporosis treatment, and their inhibitory effects on osteoclasts (OCs) have been well established. However, due to the lack of selectivity, their off-target and side effects often bring suffering to patients. Herein, an OCs' microenvironment-responsive nanoplatform HA-MC/CaCO3/ZOL@PBAE-SA (HMCZP) is developed, consisting of succinic anhydride (SA)-modified poly(ß-amino ester) (PBAE) micelle, calcium carbonate shell, minocycline-modified hyaluronic acid (HA-MC) and zoledronic acid (ZOL). Results indicate that HMCZP, as compared with the first-line therapy, could more effectively inhibit the activity of mature OCs and significantly reverse the systemic bone mass loss in ovariectomized mice. In addition, the OCs-targeted capacity of HMCZP makes it therapeutically efficient at sites of severe bone mass loss and allows it to reduce the adverse effects of ZOL, such as acute phase reaction. High-throughput RNA sequencing (RNA-seq) reveals that HMCZP could down-regulate a critical osteoporotic target, tartrate-resistant acid phosphatase (TRAP), as well as other potential therapeutical targets for osteoporosis. These results suggest that an intelligent nanoplatform targeting OCs is a promising strategy for osteoporosis therapy.

Precision Nanomedicines: Targeting Hot Mitochondria in Cancer Cells.

Mitochondrion is a multifunctional organelle in a cell, and it is one of the important targets of antitumor therapy. Conventional mitochondrial targeting strategies can hardly distinguish the mitochondria in cancer cells from those in normal cells, which might raise a concern about the biosafety. Recent studies suggest that a relatively high temperature of mitochondria exists in cancer cells. We named it tumor intrinsic mitochondrial overheating (TIMO). By taking advantage of the difference in mitochondrial temperatures between cancer cells and normal cells, therapeutic agents can be specifically delivered to the mitochondria in cancer cells. Here we will briefly overview the mitochondria-targeted delivery strategies. In addition, the recent discovery of hot mitochondria in cancer cells and the development of mitochondrial temperature-responsive delivery systems for antitumor therapy will be reviewed.

Corrigendum: Analysis of time series gene expression and DNA methylation reveals the molecular features of myocardial infarction progression.

[This corrects the article DOI: 10.3389/fcvm.2022.912454.].

Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression.

Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min, 1, 6, 24, and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs) and differentially methylated regions (DMRs) increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 min of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. Fourteen transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI.

Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer.

Reversal of cancer drug resistance remains a critical challenge in chemotherapy. Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer. To overcome the intrinsic limitations in conventional mitochondrial targeting strategies, we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin (DOX) resistance in lung cancer. Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors. As a consequence, thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice. This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.

Preparation of Lanthanide Ions-Doped BiPO4 Nanoparticles and Fe3+ Ions Assay.

A facile method for the synthesis of a Ln3+ (Eu, Tb) doped BiPO4 (BPO) nanocrystals were developed using an environment-friendly low temperature hydrothermal method assisting with phenol formaldehyde resin (PFr). Structure and surface functional groups of BPO samples were characterized by XRD and IR patterns. Morphology was studied by SEM technology also. Furthermore, doped BPO display strong red and green emissions from Eu3+ and Tb3+ ions respectively, and the BPO suspension is selectively quenched upon addition Fe3+ ions, and there is barely any interference by other metal ions, thus making the nanocrystals as a potential Fe3+ ions Fluorescent Probe, and the detection limit is below micromole level.